Jane E. Norman

Descriptive review of the evidence for the use of metformin in polycystic ovary syndrome

Use of metformin in polycystic ovary syndrome (PCOS) is becoming increasingly accepted and widespread, but clinical practice is ahead of the evidence. Although a wide range of benefits in metabolic, reproductive, and clinical measures have been reported from non-randomised trials with metformin, close inspection of results from the adequately controlled studies shows that the benefits are modest. Our aim in this descriptive review is not to define practice guidelines but to improve clinicians knowledge of the available published clinical evidence, concentrating on the few randomised controlled trials. We also highlight other issues, including hirsutism, acne, pregnancy, and neonatal outcome, that require more attention before clinical recommendations for the use of metformin in PCOS can be formalised. The potentially greater benefits achievable by lifestyle changes alone are also emphasised. We hope that the review will lead to more judicious use of metformin in PCOS and a more structured approach to research.

Term labor is associated with a core inflammatory response in human fetal membranes, myometrium, and cervix

OBJECTIVEnIdentify overlap of the transcriptome of myometrium and cervix in association with human labor.nnnSTUDY DESIGNnThe transcriptional profile of myometrial and cervical biopsies obtained from women in spontaneous labor at term (n = 9) and not in labor (n = 9) were characterized by Affymetrix v2 U133 plus 2 arrays. Common canonical pathways and functional groups were identified by Ingenuity Pathway Analysis.nnnRESULTSnOne hundred ten genes (false discovery rate < 1%) were commonly up-regulated by myometrium and cervix in association with labor and 29 genes (false discovery rate < 1%) down-regulated. Fold change in expression of up-regulated genes was strongly correlated; myometrium vs cervix (r = 0.51; P < .001), with no relationship in down-regulated genes (r = 0.26; P = .16). Canonical pathway analysis established up-regulation of inflammatory pathway signaling, with greatest increases in cellular movement and immune response gene ontology groups.nnnCONCLUSIONnGestational tissues exhibit a core inflammatory response in association with human parturition, with pathways regulating cellular trafficking dominating.

Nitric oxide donors induce ripening of the human uterine cervix: a randomised controlled trial

Objective To determine whether nitric oxide donors can induce cervical ripening before surgical termination of pregnancy in the first trimester.

Inflammatory pathways in the mechanism of parturition

Increasing evidence suggests that parturition is an inflammatory process. In this brief overview, inflammatory events occurring in association with parturition, and the mechanism by which they may contribute to labour and delivery will be discussed. Mention will be made of how this information may be of use in regulating the timing and the onset of parturition.

Cell adhesion molecule expression in the cervix and myometrium during pregnancy and parturition

Objective To determine the expression and localization of cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), E-selectin, platelet–endothelial cell adhesion molecule (PECAM), and vascular cell adhesion molecule (VCAM) in the cervix and myometrium during pregnancy and labor. Methods Biopsies of myometrium and cervix were obtained from non-pregnant women and from pregnant women before and after onset of spontaneous labor at term. Cell adhesion molecule mRNA expression was quantified using Northern blotting and cell adhesion molecule protein was localized using immunohistochemistry. Results ICAM-1 mRNA was upregulated in the cervix (10-fold increase, P < .01) and myometrium (10.5-fold increase, P < .01) during labor. ICAM-1 was localized in the vascular endothelium and in leukocytes in the cervix and myometrium from all three groups of women. VCAM mRNA was upregulated in the cervix (2.5-fold increase, P < .01) during pregnancy and there was no further change during labor. VCAM localized weakly to the vascular endothelium in cervical and myometrial biopsies from pregnant and non-pregnant women. PECAM mRNA was significantly upregulated in myometrium during pregnancy (ninefold increase, P < .01) and did not change with the onset of labor. PECAM localized to the vascular endothelium in all cervical and myometrial biopsies and was identified on leukocytes. There were no significant changes in E-selectin mRNA expression in either tissue with pregnancy or parturition. Conclusion Cell adhesion molecule expression changes in human cervix and myometrium during pregnancy and parturition. At least part of these changes are attributable to expression by leukocytes infiltrating these tissues.

Randomised trial of nitric oxide donor versus prostaglandin for cervical ripening before first-trimester termination of pregnancy

BACKGROUNDnVaginal administration of the nitric oxide donor isosorbide mononitrate can induce effective ripening of the human cervix. We investigated whether this drug is associated with fewer side-effects than prostaglandins when used to ripen the cervix before first-trimester surgical termination of pregnancy, and assessed whether the extent of cervical ripening it induces is clinically sufficient.nnnMETHODSn66 primigravid women scheduled for surgical termination were assigned to receive before surgery, per vaginam, isosorbide mononitrate 40 mg or 80 mg, or the prostaglandin analogue gemeprost 1 mg. The primary measured outcome was onset of new symptoms before termination of pregnancy.nnnFINDINGSnMore women remained symptom-free after isosorbide mononitrate than after gemeprost (28/44 [64%] vs 3/22 [14%], p<0.005). Pretreatment with gemeprost resulted in abdominal pain in 73% of women and vaginal bleeding in 32% compared with 3% and 0%, respectively, after isosorbide mononitrate, whereas, more women developed headache after isosorbide mononitrate (27%) than after gemeprost (0%). Cervical resistance and measured intraoperative blood loss were lowest after pretreatment with gemeprost. The measured cervical resistance and intraoperative blood loss with either dose of isosorbide mononitrate did not differ from those in a comparison group of 22 parous women not in the randomised trial.nnnINTERPRETATIONnPretreatment with isosorbide mononitrate to ripen the cervix before first-trimester termination of pregnancy is associated with fewer side-effects than gemeprost treatment and adequately decreases cervical resistance. Isosorbide mononitrate could be used as an alternative to gemeprost for this indication.

Nitric oxide in parturition

In 1987, Moncada and his colleagues showed that nitric oxide accounted for the biological activity of endothelium-derived relaxing factor and was responsible for the control of vascular tone.2. Since its discovery, nitric oxide has been identified as a crucial biological mediator, involved in diverse activities such as smooth muscle relaxation, neurotransmission, inflammation and regulation of the immune response3. In 1998, Furchgott, Ignarro and Murad were awarded the Nobel Prize for their contribution to science in the field of nitric oxide research. Nitric oxide is known to play a crucial role in several aspects of female reproductive physiology (for review see Chwalisz4 and Rosselli). These include menstruationand conception by means of its effects on luteinising hormone releasing hormone release9, sperm motilityI0, ovarian function-3 and implantati~n~.. Increased nitric oxide production may also be inherently involved in the normal haemodynamic changes of pregnancy, in the maintenance of the uteroplacental circulation and the control of maternal vascular tone, while a deficit of nitric oxide may contribute to the pathophysiology of intrauterine growth restriction and pre-eclampsia16J7.

Accidental out‐of‐hospital deliveries: an obstetric and neonatal case control study

Background. Accidental out‐of‐hospital (OHD) deliveries are associated with high rates of perinatal morbidity and mortality. The ability of health care workers to identify women at risk of out‐of‐hospital delivery is limited. The purpose of this study was to determine the prevalence of these deliveries in our population and to quantify the neonatal morbidity and mortality associated with such births. Further we aimed to determine whether women at risk of accidental out‐of‐hospital delivery in our population could be identified antenatally.

Randomised placebo‐controlled trial of outpatient (at home) cervical ripening with isosorbide mononitrate (IMN) prior to induction of labour – clinical trial with analyses of efficacy and acceptability. The IMOP Study

Objectiveu2002 To determine whether isosorbide mononitrate (IMN), self‐administered vaginally by women at home, improves the process of induction of labour.

A comparison of isosorbide mononitrate, misoprostol and combination therapy for first trimester pre-operative cervical ripening : a randomised controlled trial

Objective To determine whether a combined therapy with isosorbide mononitrate (40mg) and misoprostol (400μg) for pre‐operative cervical ripening in the first trimester would result in improved clinical effectiveness, and fewer side effects compared with each agent used alone.