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1.
BJOG ; 123(3): 337-45, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26301522

ABSTRACT

BACKGROUND: Second-stage caesarean section with a deeply impacted fetal head is associated with maternal and neonatal complications. OBJECTIVES: Systematic review and meta-analysis to identify, appraise and synthesise existing evidence that evaluated various techniques of delivering a baby with a deeply impacted head at full-dilation caesarean section. The primary outcome was uterine extension and secondary outcomes were other maternal and neonatal morbidities. SEARCH STRATEGY: Online searches of MEDLINE (1946-January 2015), EMBASE (1950-January 2015), Web of Sciences (1950-2015), and the Cochrane Library databases were performed using a set of relevant keywords. SELECTION CRITERIA: All studies that compared the outcome of various techniques of delivering the baby's head at full-dilation caesarean section. DATA COLLECTION AND ANALYSIS: Methodological quality was assessed using the Newcastle-Ottawa scale. Data collected from each of the studies included variables on the participants, comparisons used, and feto-maternal outcomes. Meta-analysis was performed using review manager 5.3. MAIN RESULTS: In total, 12 studies were included. Six studies (n = 455) examined primary outcomes. Meta-analysis showed that the risks of uterine incision extension, infection, mean blood loss, and operative time were significantly higher with the push technique compared with the reverse breech extraction. The evidence to support the Patwardhan method and fetal pillow was inadequate. AUTHORS' CONCLUSIONS: Evidence gathered from observational studies suggests that reverse breech extraction is associated with significantly lower maternal risks compared with the push method. TWEETABLE ABSTRACT: Meta-analysis suggests reverse breech extraction during caesarean section to deliver impacted fetus is safer.


Subject(s)
Delivery, Obstetric/methods , Obstetric Labor Complications/therapy , Cesarean Section , Female , Fetus , Head , Humans , Labor Stage, First , Pregnancy
2.
Mol Cell Endocrinol ; 407: 57-66, 2015 May 15.
Article in English | MEDLINE | ID: mdl-25766502

ABSTRACT

Bradykinin is associated with infections and inflammation, which given the strong correlation between uterine infection and preterm labour may imply that it could play a role in this process. Therefore, we investigated bradykinin signalling, and the roles that arrestin proteins play in their regulation in human myometrial cells. Bradykinin induced rapid, transient intracellular Ca(2+) increases that were inhibited following B2 receptor (B2R) antagonism. Arrestin2 or arrestin3 depletion enhanced and prolonged bradykinin-stimulated Ca(2+) responses, and attenuated B2R desensitisation. Knockdown of either arrestin enhanced B2R-stimulated ERK1/2 signals. Moreover, depletion of either arrestin elevated peak-phase p38-MAPK signalling, yet only arrestin3 depletion prolonged B2R-induced p38-MAPK signals. Arrestin2-knockdown augmented bradykinin-induced cell movement. Bradykinin stimulates pro-contractile signalling mechanisms in human myometrial cells and arrestin proteins play key roles in their regulation. Our data suggest bradykinin not only acts as an utertonin, but may also have the potential to enhance the contractile environment of the uterus.


Subject(s)
Arrestins/genetics , Bradykinin/pharmacology , Calcium/metabolism , Muscle Cells/drug effects , Arrestins/antagonists & inhibitors , Bradykinin/metabolism , Calcium Signaling , Cell Line, Transformed , Cell Movement , Female , G-Protein-Coupled Receptor Kinases/antagonists & inhibitors , G-Protein-Coupled Receptor Kinases/genetics , G-Protein-Coupled Receptor Kinases/metabolism , Gene Expression Regulation , Humans , Mitogen-Activated Protein Kinase 1/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/genetics , Mitogen-Activated Protein Kinase 3/metabolism , Muscle Cells/cytology , Muscle Cells/metabolism , Muscle Contraction/drug effects , Myometrium/cytology , Myometrium/drug effects , Myometrium/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Receptor, Bradykinin B2/genetics , Receptor, Bradykinin B2/metabolism , beta-Arrestins , p38 Mitogen-Activated Protein Kinases/genetics , p38 Mitogen-Activated Protein Kinases/metabolism
3.
Hum Reprod ; 28(8): 2058-66, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23697839

ABSTRACT

STUDY QUESTION: What are the levels of anandamide (N-arachidonoylethanolamide, AEA) in human seminal plasma and how are these related to abnormal spermatozoa? SUMMARY ANSWER: Seminal plasma AEA levels were lower in men with asthenozoospermia and oligoasthenoteratozoospermia compared with normozoospermic men. WHAT IS KNOWN ALREADY: AEA, a bioactive lipid, synthesized from membrane phospholipids may signal through cannabinoid receptors (CB1 and CB2) to regulate human sperm functions and male reproduction by modulating sperm motility, capacitation and the acrosome reaction in vitro. Local AEA levels are regulated by the synthetic and degradative enzymes, NAPE-PLD and FAAH, respectively. How the deregulation of this endogenous signalling pathway affects human sperm function(s) is not clear. STUDY DESIGN, SIZE AND DURATION: This was a cross-sectional study of 86 men presenting at an infertility clinic for semen analysis over a period of 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: AEA was quantified, by ultra-high performance liquid chromatography-tandem mass spectrometry, in seminal plasma from 86 volunteers. Using qRT-PCR, CB1, CB2, NAPE-PLD and FAAH transcript levels were determined in spermatozoa from men with normozoospermia, asthenozoospermia, oligoasthenoteratozoospermia and teratozoospermia. Normal spermatozoa were exposed in vitro to methanadamide (meth-AEA) to determine its effect on sperm motility, viability and mitochondrial activity. MAIN RESULTS AND THE ROLE OF CHANCE: Seminal plasma AEA levels (mean ± SEM) were significantly lower in men with asthenozoospermia (0.080 ± 0.01 nM; P < 0.05) or oligoasthenoteratozoospermia (0.083 ± 0.01 nM; P < 0.05) compared with normozoospermic men (0.198 ± 0.03 nM). In addition, the levels of spermatozoal CB1 mRNA were significantly decreased in men with asthenozoospermia (P < 0.001) or oligoasthenoteratozoospermia (P < 0.001) compared with normozoospermic controls. Supra-physiological levels of meth-AEA decreased sperm motility and viability, probably through CB1-mediated inhibition of mitochondrial activity. LIMITATIONS, REASONS FOR CAUTION: The inhibitory effect of meth-AEA was only shown in vitro and may not reflect what happens in vivo. WIDER IMPLICATIONS OF THE FINDINGS: As the regulation of the endocannabinoid system appears to be necessary for the preservation of normal sperm function and male fertility, there may be implications for the adverse reproductive consequences of marijuana use. Exocannabinoids, such as Δ(9)-THC, are likely to compete with endocannabinoids at the cannabinoid receptors, upsetting the finely balanced endocannabinoid signalling system. The importance of the endocannabinoid system makes it an attractive target for pharmacological interventions to control male fertility. STUDY FUNDING/COMPETING INTEREST(S): This work was funded in part by miscellaneous educational funds from the University Hospitals of Leicester National Health Services Trust to support the Endocannabinoid Research Laboratory of University of Leicester. The authors declare no competing interests.


Subject(s)
Arachidonic Acids/pharmacology , Endocannabinoids/pharmacology , Infertility, Male/pathology , Polyunsaturated Alkamides/pharmacology , Sperm Motility/drug effects , Amidohydrolases/metabolism , Arachidonic Acids/metabolism , Chromatography, High Pressure Liquid , Cross-Sectional Studies , Endocannabinoids/metabolism , Flow Cytometry , Humans , Male , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Mitochondria/physiology , Phospholipase D/metabolism , Polyunsaturated Alkamides/metabolism , RNA, Messenger/metabolism , Receptor, Cannabinoid, CB1/metabolism , Receptor, Cannabinoid, CB2/metabolism , Semen/metabolism , Spermatozoa/drug effects , Tandem Mass Spectrometry
4.
Andrologia ; 45(4): 278-84, 2013 Aug.
Article in English | MEDLINE | ID: mdl-22928818

ABSTRACT

Quantitative real-time polymerase chain reaction (qRT-PCR) has been employed to study the gene expression profiles in human spermatozoa, but accurate analysis is dependent upon normalisation of data against an endogenous control. ß-Actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are the most commonly used reference genes for normalisation of gene expression in human spermatozoa, but the expression of these genes in many tissues has considerable variation under different physiological, pathological and experimental conditions which limits their effectiveness in normalisation. The expression stability of a panel of 12 reference genes was studied in normal and pathological human spermatozoa using geNorm and NormFinder software. Although there were some discrepancies in the ranking of reference gene stability, each software program ranked B2 M, ACTB, CYC1 and 18S RNA within the top 5 and recommended the combined use of at least two reference genes. Normalisation of qRT-PCR data for the cannabinoid receptor type 2 in spermatozoa using the different housekeeping genes demonstrated how, without validation, conflicting results are obtained. We recommend that the arbitrary use of reference genes should be avoided and the validation of reference gene stability should be undertaken prior to every study. For normalisation of CB2 expression, we would recommend using the geometric mean of B2 M and ACTB.


Subject(s)
Gene Expression Profiling/standards , Infertility, Male/metabolism , Receptor, Cannabinoid, CB2/metabolism , Spermatozoa/metabolism , Humans , Male , RNA, Messenger/metabolism , Receptor, Cannabinoid, CB2/genetics , Reference Standards
5.
Matern Child Health J ; 17(4): 601-8, 2013 May.
Article in English | MEDLINE | ID: mdl-22644451

ABSTRACT

The aim of this study was to explore the relationships between nausea and vomiting in pregnancy and (a) fetal growth restriction; and (b) maternal caffeine metabolism and fetal growth restriction. A cohort of 2,643 pregnant women, aged 18-45 years, attending two UK maternity units between 8 and 12 weeks gestation, was recruited. A validated tool assessed caffeine intake at different stages of pregnancy and caffeine metabolism was assessed from a caffeine challenge test. Experience of nausea and vomiting of pregnancy was self-reported for each trimester. Adjustment was made for confounders, including salivary cotinine as a biomarker of current smoking status. There were no significant associations between fetal growth restriction and nausea and vomiting in pregnancy, even after adjustment for smoking and alcohol intake. There were no significant differences in the relationship between caffeine intake and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first (p = 0.50) or second trimester (p = 0.61) after adjustment for smoking, alcohol intake and caffeine half-life. There were also no significant differences in the relationship between caffeine half-life and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first trimester (p = 0.91) or the second trimester (p = 0.45) after adjusting for smoking, alcohol intake and caffeine intake. The results from this study show no evidence that the relationship between maternal caffeine intake and fetal growth restriction is modified by nausea and vomiting in pregnancy.


Subject(s)
Caffeine/metabolism , Fetal Development/drug effects , Fetal Growth Retardation/chemically induced , Nausea , Vomiting , Adolescent , Adult , Caffeine/administration & dosage , Female , Gestational Age , Humans , Logistic Models , Middle Aged , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, Second , Prospective Studies , Saliva/metabolism , Socioeconomic Factors , United Kingdom , Young Adult
6.
Placenta ; 32(6): 462-9, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21497900

ABSTRACT

Decidualization process involves the morphological and functional transformation of endometrial stromal cells into decidual cells. This is a finely regulated process, which involves proliferation and differentiation of stromal cells into decidual cells, which is followed by regression of the decidual tissue, mainly by apoptosis, necessary to accommodate the growing embryo. Together with the endogenous cannabinoids (ECs) and the respective metabolizing-enzymes, the cannabinoid receptors complete the endocannabinoid system (ECS). Two cannabinoid receptors have been described so far, CB1 and CB2, though a third has been suggested, CB3. Although the ECS role in several biological functions, including reproductive processes, is now well documented, the current state of knowledge about this system is still incomplete. In order to investigate the expression of GPR55, referred as the novel cannabinoid receptor 3 (CB3), in the uterine maternal tissues during normal pregnancy we analysed its expression by Q-PCR, Western blot and immunohistochemistry during fetoplacental period. We found higher protein levels on day 14, after full development of mesometrial decidua. In addition, GPR55 was found in uterine natural killer (uNK) cells pointing to an involvement in the immunological reactions that occur during pregnancy. The prominent expression of GPR55 in decidual cells suggests a role in mediating cannabinoid signalling during fetoplacental development. Additionally, we have studied the effects resulting from its activation in primary decidual cell cultures, which revealed a potential modulation of cell viability through GPR55. The data presented here may clarify the role of GPR55 in fetoplacental development and highlights the presence of a new target for cannabinoid signalling during pregnancy.


Subject(s)
Placenta/embryology , Rats/embryology , Receptors, G-Protein-Coupled/metabolism , Animals , Blotting, Western , Cell Survival , Female , Fetus , Immunohistochemistry , Pregnancy , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction
7.
Hum Reprod Update ; 17(3): 347-61, 2011.
Article in English | MEDLINE | ID: mdl-21227997

ABSTRACT

BACKGROUND: Marijuana, the most used recreational drug, has been shown to have adverse effects on human reproduction. Endogenous cannabinoids (also called endocannabinoids) bind to the same receptors as those of Δ(9)-tetrahydrocannabinol (THC), the psychoactive component of Cannabis sativa. The most extensively studied endocannabinoids are anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol. The endocannabinoids, their congeners and the cannabinoid receptors, together with the metabolic enzymes and putative transporters form the endocannabinoid system (ECS). In this review, we summarize current knowledge about the relationships of ECS, sex steroid hormones and cytokines in female fertility, and underline the importance of this endocannabinoid-hormone-cytokine network. METHODS: Pubmed and the Web of Science databases were searched for studies published since 1985, looking into the ECS, sex hormones, type-1/2 T-helper (Th1/Th2) cytokines, leukaemia inhibitory factor, leptin and reproduction. RESULTS: The ECS plays a pivotal role in human reproduction. The enzymes involved in the synthesis and degradation of endocannabinoids normalize levels of AEA for successful implantation. The AEA degrading enzyme (fatty acid amide hydrolase) activity as well as AEA content in blood may potentially be used for the monitoring of early pregnancies. Progesterone and oestrogen are involved in the maintenance of endocannabinoid levels. The ECS plays an important role in the immune regulation of human fertility. CONCLUSIONS: The available studies suggest that tight control of the endocannabinoid-hormone-cytokine network is required for successful implantation and early pregnancy maintenance. This hormone-cytokine network is a key element at the maternal-foetal interface, and any defect in such a network may result in foetal loss.


Subject(s)
Cannabinoid Receptor Modulators/physiology , Cytokines/physiology , Endocannabinoids , Fertility/physiology , Gonadal Steroid Hormones/physiology , Cannabinoid Receptor Modulators/metabolism , Female , Humans , Signal Transduction
8.
Int J Biochem Cell Biol ; 42(11): 1884-92, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20727980

ABSTRACT

The main endocannabinoids (EC) identified in mammalian tissues are N-arachidonoylethanolamide (AEA, anandamide), and 2-arachidonoylglycerol (2-AG). AEA levels are critical in pregnancy, especially during implantation, decidualization, and placental development. As 2-AG functions in pregnancy are still largely undefined, we hypothesized that it may also have a role during fetoplacental development. We showed that 2-AG is not only present in the rat mesometrial decidua and plasma during fetoplacental development, but that both 2-AG synthesizing (diacylglycerol lipase) and degradation (monoacylglycerol lipase) enzymes are expressed by decidual cells. While lower concentrations of 2-AG induced apoptosis of rat primary decidual cells, via the CB1 receptor, higher concentrations induced a dramatic effect on cell morphology, cell viability and lactate dehydrogenase release, triggered through a mechanism independent of CB1. This study provides evidences that 2-AG fluctuation in maternal tissues throughout normal pregnancy is primarily regulated by its metabolizing enzymes. Together, these data supports the hypothesis that a deregulation of the endocannabinoid system through aberrant cannabinoid signalling may impact normal uterine remodelling process and consequently normal pregnancy.


Subject(s)
Arachidonic Acids/metabolism , Glycerides/metabolism , Placentation/physiology , Uterus/metabolism , Animals , Apoptosis/genetics , Apoptosis/physiology , Blotting, Western , Cell Survival , Cells, Cultured , Decidua/cytology , Decidua/metabolism , Endocannabinoids , Female , Immunohistochemistry , Lipoprotein Lipase/genetics , Lipoprotein Lipase/metabolism , Male , Monoacylglycerol Lipases/genetics , Monoacylglycerol Lipases/metabolism , Placentation/genetics , Polymerase Chain Reaction , Pregnancy , Rats , Rats, Wistar
9.
Endocrinology ; 151(8): 3965-74, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20534733

ABSTRACT

Decidualization is essential for a successful pregnancy and is a tightly regulated process influenced by the local microenvironment. Lipid-based mediators, such as the endocannabinoid anandamide, and other compounds that have cannabimimetic actions may act on the decidua during early pregnancy. In this study, the levels of N-arachidonoylethanolamine (anandamide) and two other N-acylethanolamines, N-oleoylethanolamine and N-palmitoylethanolamine, were measured in rat plasma and maternal tissues between d 8 and 19 of pregnancy by ultraperformance liquid chromatography tandem mass spectrometry. The spatiotemporal expression of N-acylethanolamine metabolizing enzymes in implantation units were also determined by quantitative PCR, Western blot, and immunohistochemistry and shown to vary with gestation being mainly localized in decidual cells. The data also indicated that plasma and tissues levels of all three N-acylethanolamines fluctuate throughout pregnancy. Tissue levels of endocannabinoids did not correlate with plasma, suggesting that during pregnancy, maternal tissue levels of endocannabinoids are primarily regulated by in situ production and degradation to create endocannabinoid gradients conducive to successful pregnancy.


Subject(s)
Enzymes/genetics , Ethanolamines/blood , Ethanolamines/metabolism , Pregnancy/blood , Pregnancy/genetics , Amidohydrolases/genetics , Amidohydrolases/metabolism , Animals , Cannabinoid Receptor Modulators/blood , Cannabinoid Receptor Modulators/metabolism , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Decidua/metabolism , Decidua/physiology , Embryo Implantation/genetics , Embryo Implantation/physiology , Enzymes/metabolism , Female , Gene Expression Regulation, Enzymologic , Gestational Age , Phospholipase D/genetics , Phospholipase D/metabolism , Pregnancy/metabolism , Rats , Rats, Wistar , Time Factors
10.
BJOG ; 117(7): 863-9, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20406230

ABSTRACT

OBJECTIVE: Plasma anandamide (AEA) levels have previously been shown to be elevated in labour and defective cannabinoid receptor type 1 signalling in mice has been shown to be associated with elevation of corticotrophin-releasing hormone and spontaneous onset of preterm labour. We measured plasma AEA levels in women undergoing induction of labour to define the changes during the transition from the nonlabouring to labouring state. DESIGN: A longitudinal observational study. SETTING: A large UK teaching hospital. POPULATION: Term pregnant women undergoing induction of labour. METHODS: Blood was collected from women before induction of labour and again when they were in active labour. Plasma AEA was extracted and measured using ultraperformance liquid chromatography-tandem mass spectrometry. MAIN OUTCOME MEASURES: The primary outcome variable was change in plasma AEA levels from the nonlabouring to the labouring state. The secondary outcome was induction-to-delivery interval. RESULTS: There was a 1.5-fold increase in mean plasma AEA levels from 1.20 +/- 0.57 nm in the nonlabouring state to 1.82 +/- 0.87 nm in the labouring state (P < 0.0001). Induction-to-delivery interval was predicted by both Bishop's score (P < 0.0001) and percentage change in plasma AEA levels (P < 0.0001). There was a negative correlation between the percentage change in plasma AEA level and the induction-to-delivery interval (r = - 0.28; P = 0.0481). This means that the greater the rise in the plasma AEA levels the shorter the duration of labour. CONCLUSIONS: Plasma AEA levels increase with active labour and the negative correlations between percentage change in plasma AEA levels and induction-to-delivery interval suggest that AEA is likely to be involved in the physiological mechanisms of labour. Whether this increase is essential for myometrial contraction is unclear and needs further investigation.


Subject(s)
Arachidonic Acids/blood , Cannabinoid Receptor Modulators/blood , Endocannabinoids , Labor, Obstetric/blood , Polyunsaturated Alkamides/blood , Adolescent , Adult , Chromatography, Liquid , Female , Humans , Labor, Induced , Pregnancy , Young Adult
11.
BJOG ; 116(5): 637-42, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19298438

ABSTRACT

OBJECTIVE: Investigation of increased oxidative stress in early pregnancy and association with an increased risk of small-for-gestational-age (SGA) fetus. DESIGN: Longitudinal case-control study. SETTING: University Hospitals of Leicester NHS Trust, Leicester, UK. POPULATION: Low-risk pregnant women with no current or pre-existing medical illness were recruited at a large teaching hospital from 2004 to 2006. METHODS: Recruitment performed at the time of the dating ultrasound scan (12+/-2 weeks of gestation). Spot urine samples collected at 12+/-2 and 28+/-2 weeks of gestation were analysed for 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) by liquid chromatography with tandem mass spectrometry). SGA was defined as birthweight <10th centile based on customised centile calculator (www.gestation.net). This identified the cases (n=55), whereas controls (n=55) were mothers whose babies were appropriate for gestational age (AGA, birthweight 10th-90th centile). Statistical analysis was performed using GraphPad Prism v.5. The relationship between maternal urinary 8-oxodG at different gestations and customised SGA was investigated by nonparametric tests. MAIN OUTCOME MEASURES: Customised SGA and AGA pregnancies. RESULTS: Urinary 8-oxodG concentrations were significantly increased in pregnancies with subsequent SGA compared with concentrations in normal pregnancies; 12 weeks: 2.8 (interquartile range [IQR] 1.96-3.67) versus 2.2 (IQR 1.26-3.28) pmol 8-oxodG/micromol creatinine (P=0.0007); 28 weeks: 2.21 (IQR 1.67-3.14) versus 1.68 (IQR 1.16-2.82) pmol 8-oxodG/micromol creatinine (P<0.0002). Concentrations decreased significantly between week 12 and 28 (P=0.04 and P=0.02 for controls and cases). CONCLUSIONS: In this study, urinary 8-oxodG at 12 and 28 weeks were elevated in SGA compared with AGA pregnancies. This may reflect early placental changes predating clinical features of SGA.


Subject(s)
Fetal Growth Retardation/etiology , Oxidative Stress , Pregnancy/urine , 8-Hydroxy-2'-Deoxyguanosine , Adolescent , Adult , Biomarkers/analysis , Biomarkers/urine , Birth Weight , Case-Control Studies , Cotinine/analysis , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/urine , Female , Fetal Growth Retardation/metabolism , Follow-Up Studies , Humans , Pregnancy Trimester, First/urine , Pregnancy Trimester, Second/urine , Prospective Studies , Risk Assessment/methods , Saliva/chemistry , Smoking/adverse effects , Statistics, Nonparametric
12.
Obstet Gynecol Surv ; 63(5): 317-28, 2008 May.
Article in English | MEDLINE | ID: mdl-18419831

ABSTRACT

UNLABELLED: In the past 2 decades, the second trimester of pregnancy has been the most common time for prenatal diagnosis of fetal anomalies and chromosomal aneuploidies. More recently, screening for and diagnosis of chromosomal abnormalities are increasingly being performed in the first trimester. With improvements and technological advances in ultrasound, it is now possible to identify many fetal structural anomalies at 11 to 13 6/7 weeks' gestation. At 10 to 11 weeks' gestation, biochemical markers in serum-PAPP-A, free beta-hCG, AFP, and uE3-combined with sonographic measurement of nuchal translucency and the presence/absence of the nasal bone can achieve a Down syndrome detection rate of 97.5% at a false-positive rate of 5%. Structural anomalies of the central nervous system, and the cardiac, renal, and gastrointestinal tracts can now be diagnosed by either transabdominal or transvaginal scanning, achieving detection of up to 80% of CNS anomalies by 13 weeks' gestation. In future, the emphasis in prenatal diagnosis will likely be in the first trimester. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to explain the rationale for first trimester combined ultrasound and serum analyte screening for fetal Down syndrome, describe the fetal anatomic structures that can be seen and evaluated in the first trimester, provide patient counseling about the relative benefits of genetic amniocentesis versus chorionic villous sampling, and discuss the application of Doppler technology to the evaluation of a first trimester fetus.


Subject(s)
Fetal Diseases/diagnosis , Prenatal Diagnosis , Female , Humans , Pregnancy , Pregnancy Trimester, First
13.
Hum Reprod Update ; 13(5): 501-13, 2007.
Article in English | MEDLINE | ID: mdl-17584820

ABSTRACT

Maternal use of marijuana, in which the exocannabinoid Delta(9)-tetrahydrocannabinol is the most active psychoactive ingredient, is known to have adverse effects on various aspects of reproduction including ovulation, spermatogenesis, implantation and pregnancy duration. Endogenous cannabinoids of which Anandamide is the prototype are widely distributed in the body especially in the reproductive tract and pregnancy tissues and act through the same receptors as the receptor as Delta(9)-tetrahydrocannabinol. Anandamide, has been reported to have pleiotropic effects on human reproduction and in experimental animal models. It appears to be the important neuro-cytokine mediator synchronizing the embryo-endometrial development for timed implantation, the development of the embryo into the blastocyst and transport of the embryo across the fallopian tubes. The mechanisms by which it exerts these effects are unclear but could be via direct actions on the various sites within the reproductive system or its differential actions on vascular tone dependent. In this review article we bring together the current knowledge on the role of endoccanabinoids in reproduction and postulate on the potential mechanisms on how these affect reproduction. In addition, we examine its role on the endothelium and vascular smooth muscle as a potential mechanism for adverse pregnancy outcome.


Subject(s)
Arachidonic Acids/toxicity , Cannabinoid Receptor Modulators/metabolism , Embryo Implantation/drug effects , Endocannabinoids , Gametogenesis/drug effects , Marijuana Smoking , Polyunsaturated Alkamides/toxicity , Animals , Embryo, Mammalian/drug effects , Embryo, Mammalian/metabolism , Female , Humans , Pregnancy , Receptor, Cannabinoid, CB1/metabolism
14.
J Obstet Gynaecol ; 27(3): 267-70, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17464808

ABSTRACT

The management of fetal macrosomia diagnosed antenatally presents a dilemma to the obstetrician. We retrospectively reviewed the peripartum management of singleton pregnancies, which ended in the delivery of a macrosomic baby (birth weight >/=4,500 g) in our unit between 1995 and 1999. This was to determine first, the associated maternal and neonatal morbidity and second, whether the lack of consensual management in our unit influences outcome. Over the 5-year period, there were 380 macrosomic births out of 26,974 deliveries; an incidence of macrosomia of 1.4%. The mean birth weight was 4,697 +/- 330 g (range 4,500 - 5,560 g). The onset of labour was spontaneous in 234 (61.6%) cases, 120 (31.6%) were inductions and 26 (6.8%) were elective caesarean sections. Of the 354 planned vaginal deliveries, 233 (65.8%) were spontaneous, 62 (17.5%) were operative vaginal deliveries and 59 (16.7%) were emergency caesarean sections. There was no relationship between the rate of successful vaginal delivery and birth weight. There were 40 (13.6%) cases of shoulder dystocia compared with 0.9% in the non-macrosomic population (p < 0.001). Emergency caesarean sections and shoulder dystocia were significantly more common with babies weighing >/=5,000 g (28.9% vs 15.2%, p < 0.002 for caesarean section and 25.8% vs 11%, p < 0.001 for dystocia). We therefore recommend that where the estimated fetal weight is >5,000 g, an elective caesarean section should be considered. Variations in the care provided by different consultants did not have any effect on outcome. Induction for fetal macrosomia alone did not improve outcome but was associated with a significantly higher emergency caesarean section rate and should therefore be discouraged.


Subject(s)
Delivery, Obstetric/statistics & numerical data , Fetal Macrosomia/epidemiology , Fetal Macrosomia/therapy , Adolescent , Adult , Cesarean Section/statistics & numerical data , Dystocia , England/epidemiology , Female , Fetal Macrosomia/etiology , Hospitals, University , Humans , Incidence , Infant, Newborn , Obstetric Labor Complications , Pregnancy , Pregnancy Outcome
15.
BJOG ; 113(3): 318-23, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16487204

ABSTRACT

OBJECTIVE: Short telomeres are associated with adult cardiovascular disease. Our aim was to determine whether small-for-gestational-age (SGA) newborns have shortened telomeres compared with appropriately grown controls. DESIGN: Prospective cohort study. SETTING: Large tertiary referral unit in Trent, UK. POPULATION: Seventy-two women who delivered at 35-42 weeks of gestation were recruited; 34 delivered SGA babies (less than or equal to the third birthweight centile) and 38 had appropriately grown babies (greater than the tenth centile). METHODS: Maternal and cord blood samples were collected at delivery. A Southern blot of DNA from these samples was hybridised with a 32P-labelled telomeric probe and telomere length was measured. MAIN OUTCOME MEASURES: Mean maternal and newborn telomere length. RESULTS: Maternal and newborn telomere lengths were significantly correlated in both the SGA and the control groups (r2 = 0.25, P < 0.0001). Telomere lengths were similar in both maternal (control 8.41 +/- 0.9 kb versus SGA 8.29 +/- 1.0 kb, P = 0.57) and newborn (control 10.36 +/- 1.5 kb versus SGA 10.33 +/- 1.3 kb, P = 0.93) cohorts in the two groups. CONCLUSIONS: Intrauterine events associated with impaired fetal growth do not appear to be associated with increased telomere shortening.


Subject(s)
Chromosome Disorders/pathology , Fetal Growth Retardation/pathology , Infant, Small for Gestational Age/physiology , Telomere/pathology , Adult , Blotting, Southern , Case-Control Studies , Chromosome Disorders/genetics , Cohort Studies , Female , Fetal Blood/chemistry , Fetal Growth Retardation/blood , Fetal Growth Retardation/genetics , Gestational Age , Humans , Infant, Newborn , Infant, Small for Gestational Age/blood , Male , Parity , Pregnancy , Prospective Studies
16.
J Obstet Gynaecol ; 24(5): 519-20, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15369931

ABSTRACT

All cases of massive PPH (defined as estimated blood loss > 1500 ml within 24 hours of delivery) were identified from the obstetric database of the unit for the period 1997-2001 (inclusive). The casenotes of the patients were retrieved and various variables collected for analyses. Over the 5-year period, there were 145 cases of massive PPH of the 27,106 deliveries; an incidence of five per 1000 deliveries (0.5%). Most (42%) of the women were nulliparous and 12 (8%) had four or more previous deliveries. There was associated antepartum haemorrhage in 12 (8%) cases, five of which were placental abruptions. Risk factors identified to be associated with massive PPH included prolonged labour, emergency caesarean section (CS) for failure to progress, especially in the second stage (34), and placenta praevia (10). Four women had an abdominal hysterectomy. Massive PPH remains an important cause of severe maternal morbidity; risk factors, which are independent of parity, include CS in the late first stage or second stage and previous CS (irrespective of parity). A high index of suspicion is necessary for these cases, as timely intervention is more likely to minimise the complications and its consequences.


Subject(s)
Postpartum Hemorrhage/mortality , Postpartum Hemorrhage/prevention & control , Adolescent , Adult , Birth Weight , Databases, Factual , Emergency Treatment , England/epidemiology , Female , Humans , Hysterectomy , Incidence , Infant, Newborn , Medical Records , Postpartum Hemorrhage/etiology , Pregnancy , Retrospective Studies , Risk Factors
17.
J Obstet Gynaecol ; 24(3): 264-5, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15203621

ABSTRACT

To determine the outcome of induction of labour for women who had had previous caesarean sections, we identified all women who had induction of labour at the Leicester Royal Infirmary between January 1994 and September 2001. During the study period, there were 43,175 deliveries and 8761 inductions of labour (20.3%). Of these, 5047 (57.6%) were induced with prostaglandins and 138 women in this group had a previous caesarean section but eight were excluded from the analysis because of induction for early intrauterine death (five) and late terminations for fetal anomalies (three). The remaining 130 women formed the study group. Induction of labour resulted in spontaneous vaginal delivery in 50% of cases, with 11% requiring instrumental delivery and 39% had caesarean sections. There were no cases of uterine rupture in this series. We conclude that prostaglandins are safe for inducing labour in women with previous caesarean sections, but should be administered with caution.


Subject(s)
Labor, Induced/adverse effects , Uterine Rupture/epidemiology , Vaginal Birth after Cesarean , England/epidemiology , Female , Gestational Age , Hospitals, Teaching , Humans , Pregnancy , Uterine Rupture/etiology
19.
Hum Reprod ; 19(1): 179-84, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14688179

ABSTRACT

BACKGROUND: Medical treatment of endometriosis, a condition which significantly affects the quality of life in approximately 10-15% of women in the reproductive years, remains problematic. Although oral progestogens are effective and cheap, their efficacy is significantly influenced by poor compliance and systemic side effects. A progestogen (levonorgestrel) administered via an intrauterine system (Lng-IUS) has been demonstrated to improve symptoms of endometriosis; however, its effect on the staging of the disease has not been evaluated. The aims of this study were therefore to investigate the effectiveness of Lng-IUS in the symptomatic relief of minimal to moderate endometriosis and in the staging of the disease. METHODS: This was a prospective non-comparative observational study in which 34 women with clinically suspected and laparoscopically confirmed symptomatic minimal to moderate endometriosis had Lng-IUS inserted for 6 months. The symptom profile and stage of the disease before, during and after 6 months of treatment and patients' satisfaction with treatment and willingness to retain the device at the end of the study period were used to assess response to treatment. RESULTS: Of the 34 women recruited, 29 (85%) completed the study; five discontinued, for personal reasons (one), side effects of worsening of acne (one) and lower abdominal/ pelvic pain (three). Significant (P<0.05) improvements in severity and frequency of pain and menstrual symptoms as well as staging were achieved, with 68% (23) of cases electing to continue with the device after 6 months of therapy. CONCLUSION: The levonorgestrel intrauterine system is an effective hormonal option for treating symptomatic endometriosis (minimal to moderate). It also alters the American Fertility Society staging of disease. With a continuation rate of 68% after 6 months, it has the potential for providing long-term therapy in a substantial number of sufferers, although this would require further study and verification.


Subject(s)
Endometriosis/drug therapy , Endometriosis/pathology , Intrauterine Devices, Medicated , Levonorgestrel/administration & dosage , Progestins/administration & dosage , Adult , Cohort Studies , Endometriosis/physiopathology , Female , Humans , Levonorgestrel/adverse effects , Menstruation Disturbances/physiopathology , Palliative Care , Progestins/adverse effects , Severity of Illness Index , Treatment Outcome
20.
Prenat Diagn ; 23(12): 997-1002, 2003 Dec 15.
Article in English | MEDLINE | ID: mdl-14663837

ABSTRACT

OBJECTIVES: Most available data regarding accuracy of prenatal diagnosis, prevalence and outcome of congenital cystic adenomatoid malformation (CCAM) are derived largely from tertiary referral centres and may not reflect general population rates. We aimed to describe the accuracy of prenatal diagnosis, ascertain the population prevalence and post-natal outcome for cases of suspected CCAM. METHODS: Retrospective collection of prenatal and paediatric data for cases of suspected CCAM notified to the Trent Congenital Anomalies Register 1997 to 2001. RESULTS: Thirty-seven cases of CCAM were suspected prenatally. Twenty-one cases were confirmed post-natally as having a CCAM (positive predictive value 57%). Eighteen of the 21 cases were delivered at term as live births, 15 of which have undergone successful surgery to date. Thirteen of the 37 cases had apparently resolved by delivery. Three further cases were subsequently found to be cases of lung sequestration or lobar emphysema. Five cases of CCAM were detected after delivery (sensitivity of prenatal detection 81%). The population prevalence at delivery was 9.0 per 1,00,000 total births. Five confirmed cases of CCAM developed hydrops, three required in utero intervention and delivered as live births at term, one was terminated and one died in utero. The overall mortality in the confirmed cases of CCAM was 23% of which the majority were terminations of pregnancy. CONCLUSIONS: Problems of diagnostic accuracy and apparent resolution of CCAM render counselling difficult, although our data suggest that the prognosis is better than others have reported. Confirmation of the diagnosis in the neonatal period is vital in order to obtain the true population prevalence figures and to interpret outcome data.


Subject(s)
Cystic Adenomatoid Malformation of Lung, Congenital/diagnostic imaging , Cystic Adenomatoid Malformation of Lung, Congenital/epidemiology , Ultrasonography, Prenatal/standards , Adult , Cystic Adenomatoid Malformation of Lung, Congenital/embryology , Cystic Adenomatoid Malformation of Lung, Congenital/etiology , England/epidemiology , Female , Gestational Age , Humans , Medical Records , Predictive Value of Tests , Pregnancy , Pregnancy Outcome , Prevalence , Registries , Retrospective Studies , Sensitivity and Specificity
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