Fibroids and unexplained infertility treatment with epigallocatechin gallate: a natural compound in green tea (FRIEND) - protocol for a randomised placebo-controlled US multicentre clinical trial of EGCG to improve fertility in women with uterine fibroids.

Introduction: Uterine fibroids affect 30%-77% of reproductive-age women and are a significant cause of infertility. Surgical myomectomies can restore fertility, but they often have limited and temporary benefits, with postoperative complications such as adhesions negatively impacting fertility. Existing medical therapies, such as oral contraceptives, gonadotropin hormone-releasing hormone (GnRH) analogues and GnRH antagonists, can manage fibroid symptoms but are not fertility friendly.

Regulation of AMH by oocyte-specific growth factors in human primary cumulus cells.

The regulation of AMH production by follicular cells is poorly understood. The purpose of this study was to determine the role of the oocyte-secreted factors, growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), on AMH production in primary human cumulus cells. Cumulus cells from IVF patients were cultured with a combination of GDF9, BMP15, recombinant FSH and specific signaling inhibitors.

Genome-wide interactions between FSH and insulin-like growth factors in the regulation of human granulosa cell differentiation.

Study Question: Is the genome-wide response of human cumulus cells to FSH and insulin-like growth factors (IGFs) comparable to the response observed in undifferentiated granulosa cells (GCs)?

Summary Answer: FSH actions in human cumulus cells mimic those observed in preantral undifferentiated GCs from laboratory animals, and approximately half of the regulated genes are dependent on the simultaneous activation of the IGF1 receptor (IGF1R).

What Is Known Already: Animal studies have shown that FSH and the IGFs system are required for follicle growth and maturation. In humans, IGF levels in the follicular fluid correlate with patients' responses to IVF protocols.

Dynamic secretion during meiotic reentry integrates the function of the oocyte and cumulus cells.

The differentiation of the female gamete into a developmentally competent oocyte relies on the protected environment of the ovarian follicle. The oocyte plays a key role in establishing this microenvironment by releasing paracrine factors that control the functions of surrounding somatic cells. Growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are secreted during follicle growth and play pivotal roles in this local regulation.

FSH Regulates IGF-2 Expression in Human Granulosa Cells in an AKT-Dependent Manner.

Context: IGF-2 is highly expressed in the granulosa cells of human dominant ovarian follicles; however, little is known about the regulation of the IGF-2 gene or the interaction of IGF-2 and FSH during follicle development.

Objective: To examine the mechanisms involved in the regulation of the IGF-2 gene by FSH and the interplay between FSH and IGF-2 during granulosa cell differentiation. Design, Setting, Patients, and Interventions: Cumulus granulosa cells were separated from cumulus-oocyte complexes isolated from the follicular aspirates of in vitro fertilization patients and cultured for in vitro studies.

A novel "delayed start" protocol with gonadotropin-releasing hormone antagonist improves outcomes in poor responders.

Objective: To investigate whether delaying the start of ovarian stimulation with GnRH antagonist improves ovarian response in poor responders.

Design: Retrospective study.

Setting: Academic medical center.

Novel signaling mechanisms in the ovary during oocyte maturation and ovulation.

During the peri-ovulatory period, the gonadotropin LH triggers major changes in both the somatic and germ cell compartments of the ovarian follicle. The oocyte completes the meiotic cell cycle to become a fertilizable egg, and dramatic changes in gene expression and secretion take place in the somatic compartment of the follicle in preparation for follicular rupture and oocyte release. The concerted changes are regulated by activation of intracellular signaling pathways as well as paracrine and autocrine regulatory loops.

Daily compared with 8-hour gentamicin for the treatment of intrapartum chorioamnionitis: a randomized controlled trial.

Objective: To assess whether daily gentamicin is as effective as 8-hour gentamicin for the treatment of intrapartum chorioamnionitis.

Methods: Women with a clinical diagnosis of chorioamnionitis between 32 and 42 weeks of gestation were randomly assigned in labor to receive either daily gentamicin (5 mg/kg intravenously (IV), then 2 placebo doses IV after 8 and 16 hours) or 8-hour gentamicin (2 mg/kg IV, then 1.5 mg/kg IV after 8 and 16 hours).

Follicular fluid steroid hormone levels are associated with fertilization outcome after intracytoplasmic sperm injection.

Objective: To investigate the association between hormone levels from individual follicles and fertilization outcome among patients undergoing intracytoplasmic sperm injection (ICSI). Differences in concentrations of selected sex steroids and pituitary hormones in individual follicular aspirates between oocytes that fertilize successfully, those that fail to fertilize, and those that degenerate with ICSI were examined.

Design: Prospective cohort study.

The effect of follicular fluid hormones on oocyte recovery after ovarian stimulation: FSH level predicts oocyte recovery.

Background: Ovarian stimulation for assisted reproductive technology (ART) overcomes the physiologic process to develop a single dominant follicle. However, following stimulation, egg recovery rates are not 100%. The objective of this study is to determine if the follicular fluid hormonal environment is associated with oocyte recovery.

Epidermal growth factor-like growth factors in the follicular fluid: role in oocyte development and maturation.

The growth and maturation of the ovarian follicle requires the coordinate function of somatic cells and the oocyte. Over the past three decades, numerous growth factors involved in the bidirectional signals between the somatic and germ cells have been identified. A possible function of epidermal growth factor (EGF) signaling at selected stages of follicle maturation had been proposed early on and is supported by many observations of in vitro effects of this growth factor on steroidogenesis, oocyte maturation, and cumulus expansion.

Two cases of cholestasis in the first trimester of pregnancy after ovarian hyperstimulation.

Objective: To report two cases of early onset cholestasis of pregnancy associated with IVF and ovarian hyperstimulation syndrome.

Design: Case report.

Setting: University-based IVF program.

PKA-mediated phosphorylation of the beta1-adrenergic receptor promotes Gs/Gi switching.

Recently, it has been shown that PKA-mediated phosphorylation of the beta(2)-adrenergic receptor (beta(2)-AR) by the cyclic AMP-dependent protein kinase (PKA) reduces its affinity for G(s) and increases its affinity for G(i). Here we demonstrate that, like the beta(2)-AR, the beta(1)-AR is also capable of "switching" its coupling from G(s) to G(i) in a PKA-dependent manner. The beta(1)-AR is capable of activating adenylate cyclase via G(s), and can also activate the extracellular-regulated kinases, p44 and p42 (ERK1/2).

Protein kinase A-mediated phosphorylation of the beta 2-adrenergic receptor regulates its coupling to Gs and Gi. Demonstration in a reconstituted system.

While classically viewed as a prototypic G(s) and adenylyl cyclase-coupled G protein-coupled receptor, recent studies have indicated that some aspects of beta(2)-adrenergic receptor (beta(2)-AR) signaling are inhibited by pertussis toxin, indicating that they are mediated by G(i)/G(o) proteins. These signals include activation of ERK MAPKs and Akt activation, as well as hypertrophic and anti-apoptotic pathways in cardiac myocytes. Studies in cultured cells have suggested the hypothesis that protein kinase A (PKA)-mediated phosphorylation of the beta(2)-AR regulates its coupling specificity with respect to G(s) and G(i).

Selective inhibition of heterotrimeric Gs signaling. Targeting the receptor-G protein interface using a peptide minigene encoding the Galpha(s) carboxyl terminus.

The blockade of heptahelical receptor coupling to heterotrimeric G proteins by the expression of peptides derived from G protein Galpha subunits represents a novel means of simultaneously inhibiting signals arising from multiple receptors that share a common G protein pool. Here we examined the mechanism of action and functional consequences of expression of an 83-amino acid polypeptide derived from the carboxyl terminus of Galpha(s) (GsCT). In membranes prepared from GsCT-expressing cells, the peptide blocked high affinity agonist binding to beta(2) adrenergic receptors (AR) and inhibited beta(2)AR-induced [35S]GTPgammaS loading of Galpha(s).