Multivariate Markov chain analysis of the probability of pregnancy in infertile couples undergoing assisted reproduction

BACKGROUND: Estimating the probability of pregnancy leading to delivery and the influence of clinical factors on that probability is of fundamental importance in the treatment counselling of infertile couples. A variety of statistical techniques have been used to analyse fertility data, many borrowed from survival analysis. METHODS AND RESULTS: We propose an alternative method of analysis which is based on a discrete time Markov chain approach, with states 'pregnancy (leading to a delivery)', 'not pregnant', and 'censored' and in which the transition probabilities are dependent both on the clinical characteristics of the patient and the treatment given. CONCLUSIONS: We believe that the method of analysis presented here may be preferable to standard analyses in that it better reflects the clinical situation, it is a truly discrete time analysis applied to a discrete time situation, it explicitly models the censoring process (a process which in itself provides information of interest to the physician) and can be readily extended to a variety of clinical situations

Further considerations on natural or mild hyperstimulation cycles for intrauterine insemination treatment: effects on pregnancy and multiple pregnancy rates

BACKGROUND: The high iatrogenic multiple pregnancy rate associated with intrauterine insemination (IUI) in hyperstimulated cycles is becoming less acceptable. Therefore we investigated data from an earlier prospective trial with regard to the specific question of whether the application of mild hyperstimulation in IUI cycles could be an alternative strategy for obtaining acceptable pregnancy rates while preventing a high multiple pregnancy rate, compared with natural cycles for IUI. METHODS: Pregnancy outcome of 310 natural and 334 mildly hyperstimulated cycles for IUI in 171 couples with unexplained or mild male factor subfertility was analysed on a patient level with random coefficient models. RESULTS: Pregnancy rates were similar: 35 and 39.8% per couple in the natural and mildly hyperstimulated cycles respectively (P = 0.60). Multiple pregnancies, all twin pregnancies, were conceived significantly more frequently in the mild hyperstimulation group (27% of the pregnancies) than in the natural cycle group (4% of the pregnancies) (P = 0.01). All multiple pregnancies in the hyperstimulation group were conceived in multifollicular cycles. Multifollicular development was strongly associated with the application of mild hyperstimulation only (odds ratio 21.14, 95% confidence interval 8.15–54.79). CONCLUSION: The application of a mild hyperstimulation protocol as an alternative to a standard hyperstimulation protocol for IUI does not result in higher pregnancy rates than IUI in the natural cycle, while at the same time multiple pregnancies cannot be avoided. Therefore, there is no place for the use of gonadotrophins in IUI treatment

An artificially induced follicle stimulating hormone surge at the time of human chorionic gonadotrophin adminstration in controlled ovarian stimulation cycles has no effect on cumulus expansion, fertilization rate, embryo quality and implantation rate

In the spontaneous menstrual cycle, the mid-cycle gonadotrophin surge causes maturation of the cumulus-oocyte complex, mucification of cumulus cells and expansion of the cumulus oophorus, resumption of meiosis and maturation of the cytoplasm of the oocyte. Whether this is an effect purely of luteinizing hormone (LH) or whether follicle stimulating hormone (FSH) also plays a role is unknown. The effect of an artificially induced FSH surge at the time of human chorionic gonadotrophin (HCG) injection on maturation of the cumulus-oocyte complex was investigated in a prospective randomized double-blind trial. Twelve patients underwent controlled ovarian hyperstimulation [long gonadotrophin-releasing hormone agonist (GnRHa)/human menopausal gonadotrophin (HMG) protocol] for in-vitro fertilization (IVF) treatment. At the time of HCG administration, six patients received a bolus injection of FSH (450 IU i.m.); the other six patients received a placebo. The peak plasma concentrations of FSH of the experimental group were compared with the peak values of FSH obtained at the mid-cycle gonadotrophin surge of the natural cycle of a group of 12 volunteers to validate the bolus injection of FSH. Maturation of the cumulus-oocyte complex was quantified by measuring the expansion of the cumulus, by the fertilization rate and the implantation rate. The quality of the embryos was scored according the average morphology score. The bolus injection of FSH mimicked the mid-cycle gonadotrophin surge. The mean peak value of FSH (12.9 IU/l) in the experimental group was fully comparable with the mean peak value of FSH (10.0 IU/l) of the mid-cycle gonadotrophin surge in the natural cycle. No effect of a bolus injection of FSH on the maturation of the cumulus-oocyte complex or any other outcome variable was found. It is not advantageous to combine the final HCG injection with a bolus injection of FSH in GnRHa/HMG stimulated cycle

The diagnostic value of magnetic resonance imaging in differentiating benign and malignant pediatric ovarian tumors

Background The diagnostic workup of ovarian tumors in children and adolescents is challenging because preserving fertility, in addition to oncological safety, is of particular importance in this population. Therefore, a thorough preoperative assessment of ovarian tumors is required. Objective To investigate the diagnostic value of MR imaging in differentiating benign from malignant ovarian tumors in children and adolescents. Materials and methods We conducted a retrospective study of all children and adolescents age Results We included 30 girls who underwent MR imaging for an ovarian tumor. Signs indicative for malignancy were tumors with a diameter >= 8 cm, with areas of contrast enhancement, irregular margins, extracapsular tumor growth, and ascites. All benign and malignant ovarian tumors were correctly identified by the radiologists. Conclusion The diagnostic utility of MR imaging in classifying ovarian tumors in children and adolescents as benign or malignant is promising and might aid in defining the indication for ovarian-sparing versus non-ovarian-sparing surgery. We recommend evaluating these tumors with MR imaging prior to deciding on surgical treatment.Development and application of statistical models for medical scientific researc

Limited contribution of NR5A1 (SF-1) mutations in women with primary ovarian insufficiency (POI)

Item does not contain fulltextOBJECTIVE: To evaluate the significance of NR5A1 mutations in a large, well-phenotyped cohort of women with primary ovarian insufficiency (POI). Mutations in the NR5A1 gene (SF-1) were previously described in disorders of sexual development and adrenal insufficiency. Recently, a high frequency of NR5A1 gene mutations was reported in a small group of women with POI. DESIGN: Cross-sectional cohort study. SETTING: University hospital. PATIENT(S): Well-phenotyped women (n = 386) with secondary amenorrhea and diagnosed with POI, including women with familial POI (n = 77). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The entire coding region and splice sites of the NR5A1 gene were PCR-amplified and sequenced. The pathogenicity of identified mutations was predicted in silico by assessing Align-GVGD class and Grantham score. RESULT(S): Sequencing was successful in 356 patients with POI. In total, 9 mutations were identified in 10 patients. Five of these mutations concerned novel nonconservative mutations occurring in 5 patients. Prediction of effect on protein function showed low to intermediate pathogenicity for all nonconservative mutations. The overall NR5A1 gene mutation rate was 1.4%. CONCLUSION(S): The current study demonstrates that mutations in the NR5A1 gene are rare in women with POI. Primary ovarian insufficiency remains unexplained in the great majority of patients; therefore, continued efforts are needed to elucidate its underlying genetic factors.1 januari 201

“Say no to burqas”: geographies of nation and citizenship in Newtown

This thesis is concerned with the ways in which instances of everyday racism reproduce geographies of national belonging and exclusion in the city, focusing specifically on an activist campaign in Newtown, Australia, which called on the community to ‘Say no to burqas’. The focal point of this one-man campaign was a large, street facing mural, depicting a veiled woman, crossed out inside a red circle. The mural attracted much community opposition, and was defaced over sixty-four times. This thesis deconstructs the ways in which the mural campaign inscribed a particular national imaginary onto Newtown, constituted through the exclusion of the Muslim other; attending to the roots of this imaginary in racialised and gendered regimes of citizenship which privilege white, liberal civility. It goes on to show how the mural both reproduced, and was implicated in, the classed geographies of Australian multiculturalism, which figure the inner city as diverse and cosmopolitan, in opposition to the suburban as a site of ethnic criminality and multicultural failure. Finally, this thesis looks to various instances of organised opposition to the mural as examples of insurgent citizenship, capable of reimagining the relationship between place, nation and political community, in response to the ethical, political and practical task of living together in the multicultural city