OBJECTIVE: To provide the latest scientific knowledge on the efficacy of inositols for improving reproductive disorders in women with and without polycystic ovary syndrome (PCOS) and to reach a consensus on their potential use through a Delphi-like process.
METHODS: A panel of 17 endocrinologists and 1 gynecologist discussed 4 key domains: menses irregularity and anovulation, fertility, pregnancy outcomes, and neonatal outcomes.
RESULTS: A total of eight consensus statements were drafted. Myo-inositol (Myo) supplementation can be used to improve menses irregularities and anovulation in PCOS. Myo supplementation can be used in subfertile women with or without PCOS to reduce the dose of r-FSH for ovarian stimulation during IVF, but it should not be used to increase the clinical pregnancy rate or live birth rate. Myo supplementation can be used in the primary prevention of gestational diabetes mellitus (GDM), but should not be used to improve pregnancy outcomes in women with GDM. Myo can be preconceptionally added to folic acid in women with a previous neural tube defects (NTD)-complicated pregnancy to reduce the risk of NTDs in newborns. Myo can be used during pregnancy to reduce the risk of macrosomia and neonatal hypoglycemia in mothers at risk of GDM.
CONCLUSIONS: This consensus statement provides recommendations aimed at guiding healthcare practitioners in the use of inositols for the treatment or prevention of female reproductive disorders. More evidence-based data are needed to definitively establish the usefulness of Myo, the appropriate dosage, and to support the use of D-chiro-inositol (DCI) or a definitive Myo/DCI ratio.

The replication crisis has seen increased focus on best practice techniques to improve the reliability of scientific findings. What remains elusive to many researchers and is frequently misunderstood is that predictions involving interactions dramatically affect the calculation of statistical power. Using recent papers published in Personality and Social Psychology Bulletin (PSPB), we illustrate the pitfalls of improper power estimations in studies where attenuated interactions are predicted. Our investigation shows why even a programmatic series of six studies employing 2 × 2 designs, with samples exceeding N = 500, can be woefully underpowered to detect genuine effects. We also highlight the importance of accounting for error-prone measures when estimating effect sizes and calculating power, explaining why even positive results can mislead when power is low. We then provide five guidelines for researchers to avoid these pitfalls, including cautioning against the heuristic that a series of underpowered studies approximates the credibility of one well-powered study.

Ovarian hyperstimulation syndrome (OHSS) is an uncommon but serious complication associated with assisted reproductive technology (ART). This systematic review aims to identify who is at high risk, how to prevent OHSS, and the treatment for existing OHSS.

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Kisspeptins, a family of neuropeptides encoded by the Kiss1 gene that are mainly expressed in discrete neuronal populations of the hypothalamus, have recently emerged as essential upstream regulatory elements of GnRH (gonadotropin-releasing hormone) neurons and, thereby, potent elicitors of gonadotropin secretion. Indeed, kisspeptins are now recognized as important regulators of key aspects of the maturation and function of the reproductive axis, including the sexual differentiation of the brain, the timing of puberty, the adult regulation of gonadotropin secretion by gonadal hormones, and the control of fertility by metabolic and environmental (e.g., photoperiod) cues. Appreciation of these fundamental biological features has led to the contention that kisspeptins are indispensable elements of the reproductive brain whose relevance goes beyond their crucial physiological roles and may pose potential pathophysiological and therapeutic interest. In spite of such a consensus, recent developments in the field have helped to expand, and somewhat challenged, our current understanding of the neuroendocrine and molecular mechanisms whereby some of the effects of kisspeptins are conducted. This review aims to provide a synoptic and balanced account of the consensus knowledge and recent findings in the field of kisspeptin physiology, which we predict will be crucial in shaping the progress of our understanding of the roles played by this family of neuropeptides in reproductive biology.

BACKGROUND: The criteria for polycystic ovaries (PCO) as defined by the 2003 Rotterdam consensus are based on the follicle number and ovarian volume, which decrease with age. A study was performed to assess the influence of age on the PCO prevalence. In addition, the relation between follicle number and ovulation day was studied.
METHODS: Assessments were done in a spontaneous menstrual cycle in 171 healthy volunteers. The ovulation day and cycle duration were recorded. Transvaginal ultrasonography was performed between cycle day 6 and 9 to determine the follicle number and ovarian volume.
RESULTS: In the age groups between 18 and 22, 23 and 27, 28 and 32, 33 and 37, and 38 and 40 years, the prevalence of PCO was 83-84%, 66-84%, 42-79%, 19-33%, and 0-33%, respectively. Most PCO subjects had ovulatory cycles. The follicle number and ovarian volume decreased with age. There was a positive correlation between the follicle number and the ovulation day.
CONCLUSIONS: PCO were found to be very common in young women. The follicle number and ovarian volume decreased with age, and therefore also the PCO prevalence decreased with age. We believe the PCO criteria should be reconsidered and adapted to the woman\'s age. Ovulation occurred later with increasing follicle number.

Ecotoxicological hazards of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p\'-DDT) were investigated by a one-generation reproduction study using Japanese quail (Coturnix coturnix japonica) under an Organization for Economic Co-operation and Development (OECD) draft new test guideline 206 following acute and subchronic toxicity studies. In the subchronic feeding toxicity study, tremors, convulsions, and deaths were observed with a clear sex difference, males being more susceptible than females. The estimated total number of sperm tended to decrease in a dose-dependent manner at the end of 6-week treatment. In the one-generation reproduction study conducted at dose levels of 0, 6, 30, and 150 ppm, the estimated total number of sperm tended to decrease in a dose-dependent manner with a significant difference at 150 ppm. Tremors were observed in the majority of hatchlings in the 150 ppm group and at lower incidences in the 30 ppm group. Significantly high mortality rate in chicks persisted from treatment week 3-6 in the 150 ppm group and at treatment weeks 4 and 5 in the 30 ppm group. Despite of these severe adverse effects of p,p\'-DDT on hatchlings and chicks, fertilization, egg laying, eggshell thickness or embryonic development was hardly impaired by p,p\'-DDT or its metabolites. From these results, it appears that the OECD draft new avian one-generation reproduction test guideline is effective for ecological hazard assessment of chemicals.

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Little is known of the conformation of peptide hormones as they interact with their receptors for a number of reasons: peptide hormones are notoriously flexible in solution, their receptors are particularly complex, and there is strong evidence that receptor-ligand interaction leading to activation is a dynamic process. Insights into the active conformation of the decapeptide gonadotropin releasing hormone (GnRH) have been obtained previously from the solution structures of four constrained GnRH antagonists ¿cyclo(1-10)[Ac-Delta(3)-Pro(1),DCpa(2),DTrp(3,6),NMeLeu+ ++(7), betaAla(10)]GnRH (1), cyclo(4-10)[Ac-Delta(3)Pro(1),DFpa(2),DTrp(3), Asp(4),DNal(6),Dpr(10)]GnRH (2), dicyclo(4-10/5-8)[Ac-DNal(1), DCpa(2),DTrp(3),Asp(4),Glu(5),DArg(6),Lys(8),Dpr (10)]GnRH (3), and dicyclo(4-10/5-5\'-8)[Ac-DNal(1),DCpa(2),DPal(3), Asp(4),Glu(5)(Gly), DArg(6),Dbu(8),Dpr(10)]GnRH (4)¿. However, the precise location of the N-terminal tripeptide in the highly potent (K(i) < 0.4 nM) 2-4 remained unclear due to the lack of constraints in this region. The NMR structure of the newly discovered and potent (K(i) = 0.24 nM) dicyclo(1-1\'-5/4-10)[Ac-Glu(1)(Gly),DCpa(2),DTrp(3),As p(4),Dbu(5), DNal(6),Dpr(10)]GnRH (5) now allows the definition of the conformation of this region. A combined computational analysis (consensus forcing) of compounds 2-5, designed to explore the common conformations available to them that are simultaneously consistent with the NMR data corresponding to each compound, leads to a consensus structural model for the GnRH pharmacophore. This model shares some common features with the structure of the nonpeptidic GnRH mimetic T-98475. In the course of that comparative study, two additional contact points to those proposed by the authors are identified, suggesting that this model has predictive value.

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