1,721,006 research outputs found
The levonorgestrel intrauterine system: the benefits of reduced bleeding
No full textThe levonorgestrel intrauterine system (LNG-IUS) offers a new therapeutic concept that combines a highly efficient contraceptive with a treatment that reduces menstrual blood loss in both normal women and those with menorrhagia. Initially developed to decrease the risk of expulsion of the intrauterine contraceptive device by reducing myometrial contractility, recent clinical studies have shown that the LNG-IUS provides excellent contraception without many of the adverse effects associated with the conventional intrauterine contraceptive device. The main mechanism of action of the LNG-IUS appears to be at the level of the endometrium, where the high dose of local progestogen causes decidualization, epithelial atrophy and direct vascular changes. Whilst some women experience systemic hormonal effects, circulating concentrations of levonorgestrel are low in comparison to those seen after the levonorgestrel progestogen-only pill. The LNG-IUS results in a dramatic reduction in menstrual blood loss. In turn, this has led researchers to investigate the LNG-IUS as an alternative to surgery for the treatment of dysfunctional uterine bleeding, uterine fibroids and adenomyosis. The system has also been used as a means of delivering progestogen for endometrial protection in postmenopausal hormone replacement regimens. The main side-effect of the LNG-IUS is irregular breakthrough bleeding. This is most common in the first 6 months after insertion. Detailed counselling is crucial to explain this anticipated effect, in order to reduce unnecessary discontinuation of treatment. After 6 months' treatment with the LNG-IUS, 20% of women become amenorrheic, rising to 50% after 5 years. Again, it is important to explain that this is an expected phenomenon, that it is not related to disorders of the hypothalamic-pituitary-ovarian axis, and that this 'bleed-free' status might indeed be viewed as a positive feature in its own right
The Mirena(R) levonorgestrel system
No full textThe levonorgestrel intrauterine system is a safe, efficacious, long-term contraceptive device. Additionally, it results in a decrease in the volume of menstrual blood loss in women with normal periods and those with menorrhagia. It may also have a role in the treatment of other benign gynecological disorders, such as adenomyosis or endometriosis, and it has been advocated as a means of delivering progestogen to the endometrium as part of combined hormone replacement therapy. Despite the beneficial effect on menstrual volume, compliance is sometimes limited by breakthrough bleeding during the first months of use. The precise mechanism of this bleeding is unclear, but it may be related to a direct effect of levonorgestrel on endometrial vascular development. Detailed counseling is crucial to explain this anticipated side effect in order to reduce unnecessary discontinuation of treatment
Progesterone inhibits insulin-like growth factor binding protein-1 (IGFBP-1) production by explants of the Fallopian tube
No full textThe Fallopian tube provides the environment for early embryo growth, a process which is influenced by insulin-like growth factors (IGFs) in the tubal fluid. Whether the bioavailability of tubal IGFs is modulated by locally produced IGF-binding protein (IGFBP-1) is not clear. An explant culture system from human Fallopian tube mucosa was, therefore, developed enabling the potential for IGFBP-1 production by this tissue to be examined directly. Initial characterization of the system established that the explants maintained responsiveness to steroids. Thus, oviduct-specific glycoprotein production, a major product of the oviduct in vivo, continued to be made via an estrogen-sensitive pathway in the culture. The presence of mRNA for IGFBP-1 was established within the explants by the use of quantitative RT–PCR and IGFBP-1 protein was measured by enzyme-linked immunosorbent assay. Although insulin and estradiol had no consistent effect on IGFBP-1, addition of progesterone had a significant inhibitory effect on IGFBP-1 production, both at the mRNA and protein levels. A dose-range of progesterone revealed an incremental inhibitory effect of progesterone on IGFBP-1 output (maximal effect, 25–50 nmol/l), consistent with physiological inhibition of this process during the luteal phase. We suggest that progesterone might, therefore, play a role in controlling the bioavailability of IGFs to the embryo during early development within the Fallopian tube
Progesterone up-regulates WT1 mRNA and protein, and alters the relative expression of WT1 transcripts in cultured endometrial stromal cells
No full textObjectiveTo determine the change in expression of the Wilms tumor suppressor gene product, WT1, by progesterone alone in endometrial stromal cell culture and to study its relationship with prolactin, a marker of decidualization. In addition, to examine the change in ratio of WT1 isoforms with and without exon 5 message.MethodsEndometrial biopsies were taken from eight patients who had hysterectomy. Stromal cells were isolated and cultured in the presence of progesterone alone (12 days) or progesterone and 8-bromo-cyclic adenosine monophosphate (cAMP) (6 days). RNA was extracted from cells, and reverse transcription, real-time polymerase chain reaction (PCR), and conventional PCR were done to analyze WT1 mRNA expression. Immunocytochemistry was performed on equivalent cells to study WT1 protein expression. Decidualization was identified by increased prolactin concentrations in the media and immunocytochemical markers IGFBP-1 and collagen IV.ResultsReverse transcription and real-time PCR revealed a significant increase in WT1 mRNA with increasing progesterone concentrations when decidualization was occurring (n = 6, P = .002). Increasing progesterone concentrations also increased the proportion of the WT1 transcript containing a 17-amino-acid insert (+ exon 5 expression); changes in WT1 exon 5 expression have been shown to be involved in control of proliferation and differentiation. Significant correlations between WT1 message and prolactin existed at physiologic progesterone concentrations (6.25, 12.5, 25, and 50 nM; P < .05) until prolactin concentrations reached a plateau at 100 nM. At concentrations of progesterone alone (> 25 nM) and progesterone with 8-bromo-cAMP, WT1 protein was localized to the nuclei of many of the decidualized stromal cells.ConclusionThe changing expression of WT1 isoforms in endometrial stromal cells caused by progesterone may be important for differentiation into the decidualized phenotype. <br/
The ‘Developmental Origins’ hypothesis: relevance to the obstetrician and gynecologist
No full textThe recognition of ‘fetal origins of adult disease’ has placed new responsibilities on the obstetrician, as antenatal care is no longer simply about ensuring good perinatal outcomes, but also needs to plan for optimal long-term health for mother and baby. Recently, it has become clear that the intrauterine environment has a broad and long-lasting impact, influencing fetal and childhood growth and development as well as future cardiovascular health, non-communicable disease risk and fertility. This article looks specifically at the importance of the developmental origins of ovarian reserve and ageing, the role of the placenta and maternal nutrition before and during pregnancy. It also reviews recent insights in developmental medicine of relevance to the obstetrician, and outlines emerging evidence supporting a proactive clinical approach to optimizing periconceptional as well as antenatal care aimed to protect newborns against long-term disease susceptibility
Specific amino acids influence lineage differentiation in mouse blastocysts and outgrowths
No full textBlastocyst biogenesis and cell lineage differentiation into inner cell mass and trophectoderm (TE) are highly regulated processes initiated during cleavage. Cell positioning and contact patterns are well-accepted broad extrinsic factors involved in regulating blastocyst formation; however, subtle changes in the chemical composition of culture media, similarly extrinsic, may exert significant consequences for differentiation. In this study, we have examined whether, when, and how the lack of branched chain amino acids impacts on blastocyst differentiation and TE development. Using superovulated MF1 mice, embryos were flushed at 50 (2 cell) or 75 (8 cell) h after hCG and cultured in mKSOM with 0.6% BSA and amino acids at uterine fluid concentrations (Porter et al. 2003 Pediatr. Res. 53, 46A) with (all) or without (–br) the branched-chain amino acids valine, leucine, and isoleucine. Blastocysts (60 or 36 h after culture onset) were differentially labeled using the TNBS-anti-DNP-complement method with propidium iodide and Hoechst, and cells were counted on z-series with overlays using Metamorph software. For outgrowths, blastocysts developed with all aa or –br from 8 cells for 36 h were placed into KSOM supplemented with 10% FCS and either all aa or –br and cultured for an additional 120 h, scored daily, and 4?,6-diamidino-2-phenylindole nuclei counts were made at 120 h. Lack of branched amino acids from the 2-cell stage onwards caused a significant increase in total blastocyst cells with predominantly higher TE numbers, whereas, when exposed to –br from the 8 cell stage onwards, the outcome was reversed (ANOVA; Table 1). Upon outgrowth, prior amino acid composition was relatively less influential in determining spreading pattern and rate over time compared to outgrowth amino acid conditions (ANOVA; Table 1). Our data indicate that lineage development in the blastocyst is sensitive to small changes in free amino acids available and responds differently according to exposure time and duration. Subsequent development predominantly depends upon outgrowth conditions, irrespective of earlier experiences, suggesting that a similar capability for adaptive changes in response to different outgrowth media is maintained. These findings may help understand developmental plasticity and consider dynamic and potential longer-term responses to minor culture changes
Elastin distribution in the myometrial and vascular smooth muscle of the human uterus
No full textMagnetic resonance imaging and transvaginal ultrasonography in women of reproductive age suggest that the myometrium consists of inner and outer layers. It was hypothesized that these structural and functional differences in the myometrium might be associated with a variation in elastin distribution. Fifty-one hysterectomy specimens representing all phases of the normal menstrual cycle were studied by immunocytochemistry, orcein staining and image analysis. Elastin was present within the outer myometrial smooth muscle, but was less widely distributed in the inner smooth muscle. Immunoreactivity and staining were observed in the myometrial arteries and arterioles and within the basal portions of endometrial arterioles. Elastin was also present in perivascular tissue, particularly near the large vessels. More extravascular (i.e. perivascular and smooth muscle) elastin was present in the outer myometrium in all cases, although no distinct layering was observed. Semi-quantitative analysis of the elastin distribution in 11 full thickness specimens demonstrated a decreasing gradient from outer to inner myometrium rather than distinct layering. Contrary to previous reports, these data suggest that the external region of the myometrium is more elastic than the inner region and that elastin is found throughout the arteriolar tree of the human uterus
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