Contribution of myo-inositol and melatonin to human reproduction.

Diet is a critical factor for the development of both embryo and fetus, as well as maternal health. In particular, two natural molecules have been shown to exert beneficial effects on fertility, pregnancy wellness and embryo development: myo-inositol and melatonin, whose requirements increase during pregnancy. In the present review, we summarize the most important functions of melatonin and myo-inositol on male and female reproductive systems (oocyte quality and development, sperm quality), on the maintenance of a physiological pregnancy and on embryo development.

Contribution of myo-inositol to reproduction.

Myo-inositol is involved in several aspects of human reproduction. Elevated concentrations of myo-inositol in human follicular fluids appear to play a positive function in follicular maturity and provide a marker of good quality oocytes. Nevertheless its positive role in PCOS women is a consequence of a defect in the insulin signaling pathway (inositol-containing phosphoglycan mediators) that seems to be primarily implicated in the pathogenesis of insulin resistance. This article will review the involvement of inositol in female reproduction. After describing the biologic function of inositol and its derivatives, studies are quoted in which the role of inositol in fertility, oogenesis, and polycystic ovary syndrome are examined.

Methodology standards associated with quality reporting in clinical studies in pediatric surgery journals.

BACKGROUND/PURPOSE: Reports of clinical trials often lack adequate descriptions of design and analysis; recent attention has focused on improving this omission so readers can properly assess the strength of the findings and draw their own conclusions. Similar analysis of study design and methodologic standards associated with quality reporting has not been carried out for pediatric surgery journals. METHODS: All studies (n = 642) published in 1998 in Journal of Pediatric Surgery (JPS) and Pediatric Surgery International (PSI), were reviewed for demographic data and study design. The frequency of reporting of 11 basic elements of design and analysis was evaluated in randomized clinical trials (RCT), nonrandomized clinical trials (NRCT), and retrospective cohorts (RC) from JPS by consensus of 2 assessors. RESULTS: Of the 642 studies, 17% of articles (111 of 642) were classified as clinical studies. Sixty-three were comparative studies and consisted of RC (n = 48), NRCT (n = 12), and RCT (n = 3). Two-thirds of articles published were either case reports or case series (431 of 642), and 16% were basic science articles. Demographic analysis showed a wide range of topics addressed, 4 authors per article, and multiple country of origin of authors. More than 66% of all RCT in JPS reported on eligibility criteria, admission before allocation, random allocation, method of randomization, patients' blindness to treatment, treatment complications, statistical analyses, statistical methods, loss to follow-up, and statistical methods; 2 elements of design and analysis, however, were poorly reported: blind assessment of outcome (33%) and power (17%). CONCLUSIONS: There were few randomized, controlled trials in pediatric surgery journals, and further attention should be given to evaluate the causal factors. Nine elements of quality reporting were well reported; however, 2 others were poorly reported; this may improve if editors of pediatric surgical journals provide authors with guidelines on how to report clinical trial design and analysis.

Regulation of human oviductin mRNA expression in vivo.

OBJECTIVE: To examine changes in oviductin mRNA expression in oviductal mucosal tissue from fertile women throughout an ovulatory cycle. DESIGN: Semiquantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) analysis of oviductin mRNA. SETTING: University-based obstetrics and gynecology department. SUBJECT(S): Twenty women undergoing laparoscopy for tubal sterilization or hysterectomy for uterine fibroids. INTERVENTION(S): The mucosal layer was isolated from the oviduct tissue, and semiquantitative RT-PCR was performed. MAIN OUTCOME MEASURE(S): The relationship between serum estradiol, luteinizing hormone, and progesterone concentrations and the expression of oviductin mRNA. RESULT(S): There was a significant positive correlation between serum estradiol and luteinizing hormone concentrations and oviductin mRNA expression. There was a significant inverse correlation between serum progesterone concentrations and oviductin mRNA expression. CONCLUSION(S): Little is known about the regulation of human oviductin. This study was the first to examine the relationship between oviductin mRNA expression and serum estradiol and luteinizing hormone and progesterone concentrations in fertile women. Estradiol and luteinizing hormone both have a stimulatory effect on oviductin mRNA in humans, however, it is difficult to determine whether the effects are independent of one another, as the luteinizing hormone surge is dependent on the estradiol increase. Progesterone shows a clear inhibitory effect on oviductin mRNA.

Dose-finding study for the use of long-acting gonadotrophin-releasing hormone analogues prior to ovarian stimulation for IVF.

Gonadotrophin-releasing hormone (GnRH) analogues improve the outcome of treatment with IVF by increasing the number and quality of oocytes retrieved and by reducing cycle cancellation rates. Whilst short-acting GnRH analogues are most commonly used, depot preparations are now available that are more convenient for patient use. Some studies have reported that pregnancy rates with depot GnRH analogues are similar to those of short-acting preparations, but others have suggested that the more profound down-regulation seen with depot GnRH analogues results in inferior embryo quality. The purpose of this study was to determine whether a lower than conventional dose of a depot GnRH analogue may be more appropriate for use in ovarian stimulation prior to IVF. Sixty patients were randomized to receive either 3.75 mg (conventional dose) or 1.87 mg (low dose) triptorelin prior to ovarian stimulation for IVF. Suppression was measured using serum concentrations of LH measured 2 and 3 weeks after the administration of the GnRH analogues, the dose of gonadotrophin used and the time to resumption of menses. Mean concentrations of LH were 2.2 +/- 1.0 and 1.1 +/- 0.6 IU/l in the conventional dose group and 3.5 +/- 5.5 and 2.7 +/- 1.9 IU/l in the low dose group (P < 0.05 at 2 and 3 weeks). There were no significant differences between the doses of gonadotrophins used, the number of oocytes and embryos available and the time to resumption of menses, nor in the pregnancy rates. Although the degree of suppression as measured biochemically was more profound with the conventional dose, this did not affect the IVF outcome. The use of a lower dose therefore appears to be equally effective and could contribute to a reduction in the cost of treatment.

Birth of twins using in vitro matured oocytes and cryopreserved semen from a male with carcinoma of the penis.

Semen cryopreserved from a male prior to treatment for carcinoma of the penis was used for intra-cytoplasmic sperm injection (ICSI) of in vitro matured (IVM) oocytes, resulting in the birth of healthy, non-identical twin girls.

Inverse agonistic effect of ICI-174,864 on the cloned delta-opioid receptor: role of G protein and adenylyl cyclase activation.

Previous studies have established that the delta-selective antagonist ICI-174,864 exhibits negative intrinsic activity at the delta-opioid receptors in NG108-15 membranes. To determine whether ICI-174,864 can function as a true inverse agonist in intact cells, its ability to stimulate cAMP accumulation was examined in a human embryonic kidney 293 cell line (293/DOR) expressing the cloned murine delta-opioid receptor. Forskolin-stimulated cAMP accumulation in the 293/DOR cells was dose-dependently suppressed by the delta-selective agonist [D-Pen2, D-Pen5]enkephalin, and such inhibition was abolished by pertussis toxin or the opiate antagonist naloxone. In contrast, ICI-174,864 significantly potentiated the forskolin response. The ICI-174,864-induced enhancement of the forskolin response exhibited dose-dependency and was antagonized by [D-Pen2,D-Pen5]enkephalin and blocked by pertussis toxin. Neither ICI-174,864 nor pertussis toxin elevated the basal level of cAMP accumulation in the absence of forskolin. Other opiate antagonists, such as naloxone and naltrindole, were ineffective in enhancing the forskolin-stimulated cAMP accumulation. Elevation of cAMP levels in response to the activation of Gs (through either ligand-bound receptor or point mutation on alpha(s)) was also potentiated by ICI-174,864. Our results indicate that ICI-174,864 behaves as an inverse agonist in human embryonic kidney 293 cells stably expressing the delta-opioid receptor. The inverse agonistic effect of ICI-174,864 seemed to require Gi proteins and was clearly manifested when adenylyl cyclase was activated.

Activation of type II adenylyl cyclase by the cloned mu-opioid receptor: coupling to multiple G proteins.

Opioid receptors are multifunctional receptors that utilize G proteins for signal transduction. The cloned delta-opioid receptor has been shown recently to stimulate phospholipase C, as well as to inhibit or stimulate different isoforms of adenylyl cyclase. By using transient transfection studies, the ability of the cloned mu-opioid receptor to stimulate type II adenylyl cyclase was examined. Co-expression of the mu-opioid receptor with type II adenylyl cyclase in human embryonic kidney 293 cells allowed the mu-selective agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin, to stimulate cyclic AMP accumulation in a dose-dependent manner. The opioid-induced stimulation of type II adenylyl cyclase was mediated via pertussis toxin-sensitive Gi proteins, because it was abolished completely by the toxin. Possible coupling between the mu-opioid receptor and various G protein alpha subunits was examined in the type II adenylyl cyclase system. The opioid-induced response became pertussis toxin-insensitive and was enhanced significantly upon co-expression with the alpha subunit of Gz, whereas those of Gq, G12, or G13 inhibited the opioid response. When pertussis toxin-sensitive G protein alpha subunits were tested under similar conditions, all three forms of alpha i and both forms of alpha o were able to enhance the opioid response to various extents. Enhancement of type II adenylyl cyclase responses by the co-expression of alpha subunits reflects a functional coupling between alpha subunits and the mu-opioid receptor, because such potentiations were not observed with the constitutively activated alpha subunit mutants.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled ovarian hyperstimulation for in vitro fertilization using buserelin and gonadotropin in patients with previous failed cycles.

Fifteen patients who had had previous unsuccessful in vitro fertilization and embryo transfer (IVF) cycles were treated with intranasal buserelin, a gonadotropin releasing hormone agonist (GnRH-a), commencing in the mid-luteal phase prior to ovarian stimulation in the next cycle. The use of buserelin was associated with the suppression of spontaneous luteinizing hormone (LH) surges (nil versus 6), an increase in gonadotropin requirements (27.3 versus 13.7 ampoules), higher serum estradiol peak levels (8, 154 versus 4,446 pmol/l), more oocytes retrieved (87 versus 20) as well as more embryos being transferred (28 versus 7). In buserelin-treated cycles, 2 pregnancies resulted but no oocyte was recovered in 2 of the 3 poor responders.

Evaluation of a semiquantitative urinary LH assay for ovulation detection.

Levels of urinary LH were determined by a rapid, semiquantitative enzyme immunoassay dipstick test (Ovustick, now known as OvuKIT) and the results were compared with a standard serum LH double-antibody radioimmunoassay in 63 cycles of 47 women undergoing stimulated cycles for in vitro fertilisation. A good correlation was found between the two assay methods in 70% of the cycles. An increase in serum LH was associated with a concurrent rise in the dipstick measurement. Using the Ovustick method, no false-positive finding was encountered, but the LH rise was missed in one case. The number of mature oocytes aspirated was significantly higher in the stimulated cycles without an endogenous LH surge. The use of this simple and rapid enzyme immunoassay method makes possible successful and precise timing of ovulation during artificial insemination or egg retrieval for IVF in treatments for infertility.