External cephalic version at term: a cohort study of 18 years' experience.

OBJECTIVE: To analyse the outcome of referrals for external cephalic version (ECV). DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Major university hospital, UK. SAMPLE: Women with non-cephalic presentation at term and no prior caesarean, referred to a specialist clinic. METHODS: Details of referrals, ECV attempts, and perinatal outcomes were prospectively collected and analysed. Multivariate binary logistic regression models were created to determine independent predictors of ECV success, reversion, and spontaneous version. MAIN OUTCOME MEASURES: External cephalic version success rates, predictors of success and cephalic presentation at birth, and perinatal outcomes. RESULTS: Three thousand eight had confirmed breech presentation; 2614 women underwent ECV. Ineligibility for ECV occurred in 117 breech presentations (3.9%), and 297 eligible women (10.2%) declined it. ECV was successful in 1280 (49.0%, 95% CI 47.0-50.9%) (40% in nulliparous women; 64% in others); 1234 (97.3%) were cephalic at birth. Spontaneous version after failure occurred in 4.3% and was more common in multiparas (aOR 2.47, 95% CI 1.43-4.26) and those with a posterior fetal back (aOR 6.09, 95% CI 1.90-19.53). Reversion after successful ECV occurred in 2.2%. In women with a successful ECV whose fetus remained cephalic at birth, 85.7% delivered vaginally. The corrected perinatal mortality of the ECV cohort was 0.12%. CONCLUSION: External cephalic version has a low complication rate and is effective for most breech presentations, enabling vaginal birth and avoiding caesarean section. TWEETABLE ABSTRACT: External cephalic version can safely be performed with most breech presentations.

The study of progesterone action in human myometrial explants.

STUDY HYPOTHESIS: Myometrial explants represent a superior model compared with cell culture models for the study of human myometrial progesterone (P4) signalling in parturition. STUDY FINDING: Gene expression analysis showed myometrial explants closely resemble the in vivo condition and the anti-inflammatory action of P4 is not lost with labour onset. WHAT IS KNOWN ALREADY: Circulating P4 levels decline before the onset of parturition in most animals, but not in humans. This has led to the suggestion that there is a functional withdrawal of P4 action at the myometrial level prior to labour onset. However, to date, no evidence of a loss of P4 function has been provided, with studies hampered by a lack of a physiologically relevant model. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: Myometrial biopsies obtained at Caesarean section were dissected into explants after a portion was immediately snap frozen (t = 0). Microarray analysis was used to compare gene expression of t = 0 with paired (i) explants, (ii) passage 4 myometrial cell cultures or (iii) the hTERT myometrial cell line. Western blotting and chemokine/cytokine assays were used to study P4 signalling in myometrial explants. MAIN RESULTS AND THE ROLE OF CHANCE: Gene expression comparison of t = 0 to the three models demonstrated that explants more closely resemble the in vivo status. At the protein level, explants maintain both P4 receptor (PR) and glucocorticoid receptor (GR) levels versus t = 0 whereas cells only maintain GR levels. Additionally, treatment with 1 µM P4 led to a reduction in interleukin-1 (IL-1) ß-driven cyclooxygenase-2 in explants but not in cells. P4 signalling in explants was PR-mediated and associated with a repression of p65 and c-Jun phosphorylation. Furthermore, the anti-inflammatory action of P4 was maintained after labour onset. LIMITATIONS/REASONS FOR CAUTION: There is evidence of basal inflammation in the myometrial explant model. WIDER IMPLICATIONS OF THE FINDINGS: Myometrial explants constitute a novel model to study P4 signalling in the myometrium and can be used to further elucidate the mechanisms of P4 action in human labour. LARGE SCALE DATA: Data deposited at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=gvmpggkurbgxfqf&acc=GSE77830. STUDY FUNDING AND COMPETING INTEREST: This work was supported by grants from the Joint Research Committee of the Westminster Medical School Research Trust, Borne (No. 1067412-7; a sub-charity of the Chelsea and Westminster Health Charity) and the Imperial NIHR Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS or the Department of Health. The authors have no conflict of interest.

Progesterone and the Repression of Myometrial Inflammation: The Roles of MKP-1 and the AP-1 System.

Progesterone (P4) maintains uterine quiescence during pregnancy and its functional withdrawal is associated with increased prostaglandin synthesis and the onset of labor. In primary human myometrial cells, the glucocorticoid receptor (GR) rather than the P4 receptor mediates P4 antagonism of IL-1ß-induced cyclooxygenase-2 (COX-2) expression, the rate-limiting enzyme in prostaglandin synthesis. We now report that P4 also acts via GR to induce MAPK phosphatase (MKP)-1 and knockdown of MKP-1 impairs the ability of P4 to repress IL-1ß-dependent COX-2 induction. Microarray analysis revealed that P4 repressed preferentially activator protein-1-responsive genes in response to IL-1ß. Consistent with these observations, we found that the ability of P4 to reduce c-Jun activation was lost upon GR as well as MKP-1 knockdown. Interestingly, c-Jun levels in human myometrial cells declined upon GR and MKP-1 knockdown, which suggests the presence of an activator protein-1 feedback loop. This is supported by our observation that c-Jun levels declined after an initial rise in primary myometrial cells treated with phorbol 12-myrisatate 13-acetate, a potent activator of c-Jun N-terminal kinase. Finally, we show that MKP-1 is an intermediate in P4-mediated repression of some but not all IL-1ß-responsive genes. For example, P4 repression of IL11 and IRAK3 was maintained upon MKP-1 knockdown. Taken together, the data show that P4 acts via GR to drive MKP-1 expression, which in turn inhibits IL-1ß-dependent c-Jun activation and COX-2 expression.

Streamlining outpatient urogynaecology: a novel approach.

With population ageing, service expansion in urogynaecology is a necessity. The aim of this study was to determine the feasibility of a nurse specialist-led triage clinic as a novel way of outpatient care provision. Review of the patient pathway through the service over a 15-month period demonstrated effective patient management with timely order of investigations and treatment initiation, improved continuity of care, a reduction in the volume of medical consultations and high patient satisfaction. In conclusion, specialist nurse clinics provide a sustainable method of service expansion, while simultaneously facilitating service transfer to the community in line with current healthcare policy.