Multifaceted intervention to improve obstetric practices: The OPERA cluster-randomized controlled trial.

OBJECTIVE: Suboptimal care contributes to perinatal morbidity and mortality. We investigated the effects of a multifaceted program designed to improve obstetric practices and outcomes. STUDY DESIGN: A cluster-randomized trial was conducted from October 2008 to November 2010 in 95 French maternity units randomized either to receive an information intervention about published guidelines or left to apply them freely. The intervention combined an outreach visit with a morbidity/mortality conference (MMC) to review perinatal morbidity/mortality cases. Within the intervention group, the units were randomized to have MMCs with or without clinical psychologists. The primary outcome was the rate of suboptimal care among perinatal morbidity/mortality cases. The secondary outcomes included the rate of suboptimal care among cases of morbidity, the rate of suboptimal care among cases of mortality, the rate of avoidable morbidity and/or mortality cases, and the incidence of, morbidity and/or mortality. A mixed logistic regression model with random intercept was used to quantify the effect of the intervention on the main outcome. RESULTS: The study reviewed 2459 cases of morbidity or mortality among 165,353 births. The rate of suboptimal care among morbidity plus mortality cases was not significantly lower in the intervention than in the control group (8.1% vs. 10.6%, OR [95% CI]: 0.75 [0.50-1.12], p=0.15. However, the cases of suboptimal care among morbidity cases were significantly lower in the intervention group (7.6% vs. 11.5%, 0.62 [0.40-0.94], p=0.02); the incidence of perinatal morbidity was also lower (7.0 vs. 8.1‰, p=0.01). No differences were found between psychologist-backed and the other units. CONCLUSIONS: The intervention reduced the rate of suboptimal care mainly in morbidity cases and the incidence of morbidity but did not succeed in improving morbidity plus mortality combined. More clear-cut results regarding mortality require a longer study period and the inclusion of structures that intervene before and after the delivery room. (ClinicalTrials.gov ID: NCT02584166).

Clinical audit: a useful tool for reducing severe postpartum haemorrhages?

OBJECTIVE: Reducing the rate of severe postpartum haemorrhage (PPH) is a major challenge in obstetrics today. One potentially effective tool for improving the quality of care is the clinical audit, that is, peer evaluation and comparison of actual practices against explicit criteria. Our objective was to assess the impact of regular criteria-based audits on the prevalence of severe PPH. DESIGN: Quasi-experimental before-and-after survey. SETTING: Two French maternity units in the Rhône-Alpes region, with different organization of care. PARTICIPANTS: All staff of both units. INTERVENTION: Quarterly clinical audit meetings at which a team of reviewers analysed all cases of severe PPH and provided feedback on quality of care and where all staff actively participated. MAIN OUTCOME MEASURES: The primary outcome was the prevalence of severe PPH. Secondary outcomes included the global quality of care for women with severe PPH, including the performance rate for each recommended procedure. Differences in these variables between 2005 and 2008 were tested. RESULTS: The prevalence of severe PPH declined significantly in both units, from 1.52 to 0.96% of deliveries in the level III hospital (P = 0.048) and from 2.08 to 0.57% in the level II hospital (P < 0.001). From 2005 to 2008, the proportion of deliveries with severe PPH that was managed consistently with the guidelines increased for all of its main components, in both units. CONCLUSION: Regular clinical audits of cases severe PPH were associated with a persistent reduction in the prevalence of severe PPH.

Turner syndrome and pregnancy: clinical practice. Recommendations for the management of patients with Turner syndrome before and during pregnancy.

Following the death in France by acute aortic dissection of two women with Turner syndrome who were pregnant following oocyte donation, the Director of the French Biomedicine Agency (Agence de la biomédecine) sent a letter to the President of the French College of Obstetricians and Gynaecologists (FCOG). He requested the College's expertise in reviewing point-by-point the cases and risk factors and in determining whether there are grounds to propose additional measures complementary to the recommendations made by the Haute autorité de santé or French National Authority for Health (HAS) in 2008 in terms of indication and monitoring of patients. A joint practice committee of the FCOG, the French Cardiologic Society, the French Chest and Cardiovascular Surgery Society, the French Society of Anaesthesia and Intensive Care, the French Endocrine Society, the French study group for oocyte donation, and the Biomedicine Agency defined the exact questions to be put to the experts, chose these experts, followed them up and drafted the synthesis of recommendations resulting from their work. The questions concerned the check-up before pregnancy of Turner patients, contraindication and acceptance of pregnancy, information for the patients, and recommendations for antenatal care, delivery and postnatal follow-up.

Fetal Doppler Hypoxic index for the prediction of abnormal fetal heart rate at delivery in chronic fetal distress.

OBJECTIVE: To design a Doppler Hypoxic index (HI), which takes into account both the duration and the intensity of fetal flow redistribution (i.e. hypoxia) for predicting the occurrence of abnormal fetal heart rate (FHR) at delivery. METHOD: Sixty-six pregnancies with hypertension and/or growth retardation (IUGR) were investigated (age: 23+/-5 years; primigravidas: 30%, CS 59%; hospitalisation: 10+/-8 days, IUGR (<10 c) 82%, intensive care 23%, fetal death 1). Umbilical (URI) and cerebral (CRI) Doppler resistance indices, and the C/U ratio (CRI/URI) were measured every 2 days from admission to delivery. HI was calculated by summing the daily %C/U reduction (in % from normal cut-off limit 1.1) over the period of observation (or mean C/U reduction in % from 1.1 x number of days of observation). Doppler C/U and HI were compared with fetal heart rate (FHR) traces, and perinatal data. RESULTS: HI > 160% was associated with abnormal FHR in 80% of the cases (PPV = 87%, NPV = 88%). HI > 160% predicted the occurrence of abnormal FHR 8+/-6 days before they happened. CONCLUSION: A combination of intensity and duration of the fetal flow redistribution (i.e. hypoxia) evaluated by Doppler is correlated with the occurrence of abnormal fetal heart rate.

[Identification and management of hereditary predisposition to cancer of the breast and the ovary (update 2004)]. / Identification et prise en charge des prédispositions héréditaires aux cancers du sein et de l'ovaire (mise à jour 2004).

BACKGROUND: Since the last recommendations, up to 2,500 new references had been published on that topic. METHODOLOGY: On the behalf of the health Minister, the Ad Hoc Committee consisted of 13 experts carried out a first version revisited by five additional experts who critically analyzed the first version of the report. MAIN UPDATING: Breast and ovarian cancer seem to be associated with fewer deleterious mutation of BRCA12 and BRCA2 than previously thought. The screening of ovarian cancer is still not an attractive option while in contrast MRI may be soon for these young women with dense breast, the recommended option for breast cancer screening. The effectiveness of prophylactic surgeries is now well established. French position is to favor such surgeries with regard to a quality of life in line with the expected benefit, and providing precise and standardized process described in the recommendation. CONCLUSIONS: Due to methodological flaws, the low power and a short follow-up of the surveys, this statement cannot however aspire to a high stability.

Overnight incubation improves selection of frozen-thawed blastocysts for transfer: preliminary study using supernumerary embryos.

A study was undertaken to determine whether the interval between thawing and transfer influences both biological and clinical outcomes of cryopreserved blastocysts, using supernumerary embryos cultured in sequential media. One hundred and seventy-two patients who underwent blastocyst thawing without any exclusion criteria were included in this single center prospective study of blastocyst thawing cycles. Outcome of 338 blastocysts originating from culture of supernumerary embryos in sequential media was analyzed after 4 or 20 h of culture between thawing and transfer. Survival rate, re-expansion and hatching rates for surviving blastocysts, implantation rates (IRs), pregnancy and miscarriage rates were studied. Blastocyst survival was not influenced by the incubation time after thawing; however both re-expansion and hatching rates were increased after 20-h incubation. Moreover, the IR per thawed or transferred blastocyst was increased three-fold after 20-h incubation compared to 4-h incubation. Increasing the interval between thawing and transfer appears to be beneficial in order to better select for transfer frozen-thawed blastocysts.

Risk factors for cervical stenosis after laser cone biopsy.

OBJECTIVE: To evaluate the incidence of cervical stenosis after laser cone biopsy and to identify risks factors for this adverse outcome. METHODS: Prospective study evaluating all patients (n = 375) treated by laser cone biopsy for suspected cervical intraepithelial neoplasia between 1 January 1990 and 31 December 1996. Patients were contacted by mail for a clinical evaluation, 37 +/- 26 months after surgery. Two hundred and thirty-eight patients (63%) reply to this clinical follow-up examination including colposcopy, cervical smear and evaluation of cervical stenosis. Cervical stenosis was defined as cervical os narrowing preventing the insertion of a cotton swab. RESULTS: Forty patients (16.8%) had cervical stenosis at follow-up. The risk of postoperative cervical stenosis increases when patients were older (mean age of women with stenosis 42 years versus 35 years; P < 0.0001), when the depth of surgical excision increases (mean surgical specimen height 18.2 mm in women with stenosis versus 15.9 mm; P < 0.01), when preoperative junction was endocervical (2.5; 95% confidence interval (CI) 1.4-4.7), when vaginal packing was necessary (2.4; 95% CI 1.4-4.2), and when continuous laser mode was used (2.1; 95% CI 1.2-3.7). Stenosis incidence was lower when human papilloma virus (HPV) was present on cervical biopsy (0.47; 95% CI 0.3-0.8), when women were smokers (0.48; 95% CI 0.3-0.9), and when a Surgicel compress was placed in the excision site (0,4; 95% CI 0.2-0.8). Patient age was the only significant independent predictor of stenosis identified by a multivariate analysis using logistic regression. CONCLUSIONS: Patient with advanced age should be counselled regarding the risks for cervical stenosis after laser cone biopsy. Other surgical options may be considered when patient age exceeds 40 years.

[Standards, Options and Recommendations 2000: non metastatic endometrial cancer]. / Standards, Options et Recommendations 2000: cancer de l'endomètre, stades non métastatiques (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Cancer Centers, and specialists from French Public Universities, General Hospitals and Private Clinics, and some specialists learned societies. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The SORs are developed using a methodology based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for the management of patients with carcinoma of the endometrium according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 63 independent reviewers. RESULTS: The main recommendations for the management of carcinoma of the endometrium are: 1) The diagnosis of carcinoma of the endometrium is based on biopsy and histological examination. However, as first intention, the first elements for diagnosis can be obtain from a hysterography, or particularly, a endovaginal ultrasound examination. Ultrasound allows locoregional metastases to be detected, the CT scan allows the lymph node involvement to be assessed and magnetic resonance imaging allows the myometrium invasion to be evaluated. 2) For the majority of patients, surgery is the initial treatment, both for localised and advanced-stage carcinomas. The excised sample can be used for pathological analysis and tumour staging, using the FIGO (Fédération internationale de gynécologie obstétrique) classification. Surgery for patients with stage I and II carcinomas involves total extrafascial hysterectomy with bilateral salpingo-oophorectomy., In patients with stage III and IV carcinomas radical surgery should be performed, when possible. If this is not possible, then surgery should be as complete as possible and be associated with a complementary treatment. In patients with the most advanced carcinomas, tumour reduction by surgery should be performed. 3) Complementary treatment includes external-beam radiotherapy and brachytherapy. The decision concerning the extent and type of irradiation should be taken taking into consideration the stage and the prognostic factors present. For patients with stage I and II carcinoma, complementary treatment with brachytherapy can be performed, if the myometrium invasion is not deep, or if the carcinoma is grade 2 or 3. Patients with stage III carcinomas can be treated with pelvic or abdominal-pelvic complementary irradiation. In patients that cannot undergo surgery, exclusive radiotherapy can be performed. 4) In the absence of any symptoms, surveillance should include a general clinical and gynaecological examination. All patients with symptoms should undergo an additional work-up.

Sonohysterography: a prospective survey of results and complications in 81 patients.

PURPOSE: To evaluate the sonohysterography (SHG) for the diagnosis of intrauterine abnormalities and describe complications and failure rate. STUDY DESIGN: A prospective survey on 81 patients, (44 patients with menometrorrhagia, 30 with postmenopausal bleeding and 7 with infertility) was conducted. Histopathology and clinical survey, if sonohysterography was normal, were the gold standards. RESULTS: Pathology has been performed in 55 cases. There were four failures (cervical stenosis), one severe complication (endometritis), one pelvic pain. Sensitivity and specificity of sonography were 56 and 83%; for sonohysterography 88 and 98%; and for hysteroscopy 78 and 97%. Sonohysterography was accurate for the diagnosis of the submucous myoma component. CONCLUSION: Sonohysterography is available in uterine pathology, easy, safe and cheap, but sonographists and patients should be informed of the little risks of such examination technique.

Apoptosis, onset and maintenance of spermatogenesis: evidence for the involvement of Kit in Kit-haplodeficient mice.

Kit/stem cell factor (SCF ) has been reported to be involved in survival and proliferation of male differentiating spermatogonial cells. This kinetics study was designed to assess the role of Kit/SCF during spermatogenesis in mice, and the extent of male programmed germ cell death was measured between 8 and 150 days of age. For this purpose, 129/Sv inbred mice in which one Kit allele was inactivated by an nlslacZ sequence insertion (Kit(W-lacZ/+)) were compared with 129/Sv inbred mice with wild-type alleles at the Kit locus. Four different approaches were used: 1) morphometric study to assess spermatogenesis, 2) flow cytometry to study testicular cell ploidy, 3) in situ end labeling to detect apoptosis, and 4) follow-up of reporter gene expression. Spermatogenesis was lower in Kit(W-lacZ/+) heterozygous mice both at the onset of spermatogenesis and during adulthood. Indeed, greater apoptosis occurred at the onset of spermatogenesis. This was followed in the adult by a smaller seminiferous tubule diameter and a lower ratio between type B spermatogonia and type A stem spermatogonia in Kit(W-lacZ/+) mice compared with Kit(+/+) mice. These differences are probably related to the Kit haplodeficiency, which was the only difference between the two genotypes. Germ cell counts and testicular cell ploidy revealed delayed meiosis in Kit(W-lacZ/+) mice. Reporter gene expression confirmed expression of the Kit gene at the spermatogonial stage and also revealed Kit expression during the late pachytene/diplotene transition. These results suggest involvement of Kit/SCF at different stages of spermatogenesis.

Cohort follow-up of couples with primary infertility in an ART programme using frozen donor semen.

BACKGROUND: This study was designed to determine the crude cumulative live-birth rates in a cohort initiating frozen donor semen treatment until completion. METHODS: This cohort study included 588 couples with primary infertility in one University Hospital centre. The treatment sequence involved first artificial insemination (AID) followed by IVF if necessary (IVF-D). Live birth, drop-out for personal or medical reasons and recourse to IVF-D were recorded for all patients. Live births and drop-out were expressed both as rates per cycle and crude cumulative rates. RESULTS: At the completion of AID and IVF-D cycles, 406 couples in the cohort (69%) achieved a live-birth and 182 couples (31%) discontinued treatment. In most cases, couples stopped treatment for personal reasons (74%) whereas fewer couples were denied further treatment for medical reasons (26%). CONCLUSIONS: This is the first report on the crude cumulative live-birth rate in a cohort after AID and IVF-D cycles. Although calculation based on crude cumulative live-birth rate shows lower results in comparison with life table analysis, this method allows patients to obtain an insight into their actual chances of achieving a successful pregnancy.

Parameters guiding selection of best embryos for transfer after cryopreservation: a reappraisal.

BACKGROUND: The purpose of this study was to evaluate the respective influences of blastomere survival and resumption of mitosis on the outcome of frozen-thawed embryos. METHODS: A retrospective analysis was performed in our centre on 363 thawing cycles, involving 4-cell day 2 grade 1 embryos with <10% fragmentation. RESULTS: A higher implantation rate per transferred embryo was observed when all transferred embryos were characterized by fully intact blastomeres (100% blastomere survival) as compared with damaged embryos (50 or 75% blastomere survival) (22.0 versus 7.2%; P < 0.0001). Moreover, the implantation rate per transferred embryo was significantly higher for cleaved embryos compared with uncleaved embryos (19.7 versus 3%; P < 0.0001). Transfer of fully intact, cleaved embryos resulted in the highest implantation rates compared with transfer of damaged and uncleaved embryos (27.4 versus 0%; P < 0.0001). Intermediate implantation rates were observed when only one of the two criteria was fulfilled (13 versus 11% respectively; P > 0.05). Multivariate analysis showed that the clinical pregnancy rate was influenced by both criteria (odds ratio = 3.4 for transfer of embryos with six or more cells versus embryos with less than six cells. CONCLUSION: The results of our study suggest that the most important factor to predict further embryo development is the total number of blastomeres in transferred embryos, however they are obtained (good survival and/or resumption of mitosis).