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Polanski L.T.,Nurture Fertility | Barbosa M.A.P.,University of Sao Paulo | Martins W.P.,University of Sao Paulo | Baumgarten M.N.,Nurture Fertility | And 4 more authors.
Human Reproduction | Year: 2014

STUDY QUESTION: Is there any scientific evidence to support the routine use of adjuvant therapies for women with elevated natural killer (NK) cells undergoing assisted reproduction techniques (ARTs) in order to improve live birth rate? SUMMARY ANSWER: Due to the poor quality evidence, this review does not support the use of described adjuvant treatments in women found to have elevated absolute numbers or activity of NK cells undergoing ART. WHAT IS KNOWN ALREADY: Deregulation in the numbers of NK cells and/or their activity, in the blood as well as in the endometrium, has been associated with various manifestations of reproductive failure. NK cell analysis is becoming increasingly popular as a test offered to investigate the causes of reproductive failure. Adjuvant therapies influencing the NK cells have been postulated as therapeutic options for couples where deregulation of this component of the maternal immune system is suspected as the cause of infertility or implantation failure. STUDY DESIGN, SIZE, DURATION: Systematic review. Embase, LILACS, MEDLINE, PsycINFO, CENTRAL and CINAHL databases from 1946 to present were searched with no language restrictions. PARTICIPANTS/ MATERIALS, SETTING, METHODS: Studies evaluating the use of adjuvant therapies in women undergoing ART where NK cell numbers and/or activity were assessed were considered eligible for inclusion. MAIN RESULTS AND THE ROLE OF CHANCE: Only three studies (one in abstract form only) meeting the inclusion criteria were identified: two reported the use of intravenous immunoglobulins (IVIg) and one the use of oral prednisolone. All studies demonstrated a beneficial effect of the interventions on clinical pregnancy rates with a risk ratio (RR) of 1.63 [95% confidence interval (CI) 1.00-2.66] for prednisolone and 3.41 (95%CI 1.90-6.11) for IVIg. Studies assessing the efficacy of IVIg have also reported live birth rate with an RR of 3.94 (95% CI 2.01-7.69) favoring the intervention. Data heterogeneity was substantial however (I2 = 66%) suggesting a cautious interpretation of the results. LIMITATIONS, REASONS FOR CAUTION: Differing study populations, lack of statistical power, method of data presentation (per couple or per cycle), the use of additional medications and differing dosage regimes contribute to data heterogeneity and suggest a cautious approach to data interpretation. WIDER IMPLICATIONS OF THE FINDINGS: This review identified some data showing that adjuvant therapies (mainly IVIg) in this selected population seem to confer some benefit on ART outcome. However, overall, the review does not support the use of prednisolone, IVIg or any other adjuvant treatment in women undergoing ART who are found to have elevated absolute numbers or activity of NK cells, purely due to the paucity of, or poor quality of, the evidence. Agreement as to the most reliable NK cell testing method must be made by the scientific community as well as 'normal' NK cell levels unequivocally defined. Well designed, sufficiently powered RCTs with an appropriate population selection and using the same NK cell testing methodology are required to ascertain the actual benefit of using adjuvant therapy treatment for elevated NK cell levels or activity in the context of pregnancy outcome following IVF. STUDY FUNDING/COMPETING INTEREST(S): None. © The Author 2013. Source


Polanski L.T.,University of Nottingham | Baumgarten M.N.,University of Nottingham | Brosens J.J.,University of Warwick | Quenby S.M.,University of Warwick | And 3 more authors.
Ultrasound in Medicine and Biology | Year: 2015

Our aim in the study described here was to assess the feasibility of spatiotemporal image correlation power Doppler quantification of the endometrium with two techniques: spherical samples and whole tissue. We scanned 51 women in the midluteal phase of the menstrual cycle: STIC assessment of the whole endometrium was not possible in 10% of cases, whereas spherical analysis was possible in all. The time taken for data set analysis was much longer for the whole endometrium compared with spherical analysis (1478.9 ± 291 s vs. 266.8 ± 39.3 s, p < 0.05). Intra-class correlation coefficients for the vascularization flow index (VFI) were similar for both methods. Volumetric vascularity indices were higher when spherical sampling was conducted. Significant cycle-to-cycle variability in the vascularity indices was present, with coefficients of variation exceeding 20% for both techniques. We found that STIC power Doppler quantification of the whole endometrium is possible in the majority of cases, however, it is time consuming and limited by significant cycle-to-cycle variability. © 2015 World Federation for Ultrasound in Medicine and Biology. Source


Richardson A.,Nurture Fertility | Richardson A.,University of Nottingham | Gallos I.,University of Birmingham | Dobson S.,University of Nottingham | And 4 more authors.
Ultrasound in Obstetrics and Gynecology | Year: 2015

Objectives To evaluate the diagnostic accuracy of ultrasound in predicting the location of an intrauterine pregnancy before visualization of the yolk sac is possible. Methods This was a systematic review conducted in accordance with the PRISMA statement and registered with PROSPERO. We searched MEDLINE, EMBASE and The Cochrane Library for relevant citations. Studies were selected in a two-stage process and their data extracted by two reviewers. Accuracy measures were calculated for each ultrasound sign, i.e. gestational sac, double decidual sac sign, intradecidual sign, chorionic rim sign and yolk sac. Individual study estimates were plotted in summary receiver-operating characteristics curves and forest plots for examination of heterogeneity. The quality of included studies was assessed. Results Seventeen studies including 2564 women were selected from 19 959 potential papers. Following meta-analysis, the presence of a gestational sac on ultrasound examination was found to predict an intrauterine pregnancy with a sensitivity of 52.8% (95% CI, 38.2-66.9%) and specificity of 97.6% (95% CI, 94.3-99.0%). The corresponding performance of the double decidual sac sign, intradecidual sign, chorionic rim sign and yolk sac were: 81.8% (95% CI, 68.1-90.4%) and 97.3% (95% CI, 76.1-99.8%); 66.1% (95% CI, 58.9-72.8%) and 100% (95% CI, 91.0-100%); 79.9% (95% CI, 73.0-85.7%) and 97.1% (95% CI, 89.9-99.6%); and 42.2% (95% CI, 27.7-57.9%) and 100% (95% CI, 54.1-100%), respectively. Conclusion Visualization of a gestational sac, double decidual sac sign, intradecidual sign or chorionic rim sign increases the probability of an intrauterine pregnancy but is not as accurate for diagnosis as the detection of the yolk sac. However, the findings were limited by the small number and poor quality of the studies included and heterogeneity in the index test and reference standard. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. Source


Richardson A.,Nurture Fertility | Richardson A.,University of Nottingham | Gallos I.,University of Birmingham | Dobson S.,University of Nottingham | And 4 more authors.
Ultrasound in Obstetrics and Gynecology | Year: 2016

Objectives To determine the accuracy of ultrasound in the diagnosis of a tubal ectopic pregnancy in the absence of an obvious extrauterine embryo. Methods This was a systematic review conducted in accordance with the PRISMA statement and registered with PROSPERO. We searched MEDLINE, EMBASE and The Cochrane Library for relevant citations from database inception to July 2014. Studies were selected in a two-stage process and their data extracted by two reviewers. Accuracy measures were calculated for each ultrasound sign, i.e. empty uterus, pseudosac, adnexal mass and free fluid in the pouch of Douglas, alone and in various combinations. Individual study estimates were plotted in summary receiver-operating characteristics curves and forest plots for examination of heterogeneity. The quality of included studies was assessed. Results Thirty-one studies including 5858 women were selected from 19 959 citations. Following meta-analysis, an empty uterus on ultrasound was found to predict an ectopic pregnancy with a sensitivity of 81.1% (95% CI, 42.1-96.2%) and specificity of 79.5% (95% CI, 68.9-87.1%). The corresponding performance of the pseudosac, adnexal mass and free fluid were: 5.5% (95% CI, 3.3-9.0%) and 94.2% (95% CI, 75.9-98.8%); 63.5% (95% CI, 48.5-76.3%) and 91.4% (95% CI, 83.6-95.7%); and 47.2% (95% CI, 33.2-61.7%) and 92.3% (95% CI, 85.6-96.0%), respectively. Conclusion Visualization of an empty uterus, adnexal mass, free fluid or a pseudosac has poor sensitivity for the diagnosis of a tubal pregnancy when an obvious extrauterine embryo is absent, but it has good specificity. We can therefore infer that ultrasound is more useful for 'ruling in' a tubal pregnancy than 'ruling out' one. However, the findings were limited by the poor quality of some included studies and heterogeneity in the index test and reference standard. © Copyright 2015 ISUOG. Published by John Wiley & Sons Ltd. Source


Richardson A.,Nurture Fertility | Richardson A.,University of Nottingham | Brearley S.,Nurture Fertility | Ahitan S.,Nurture Fertility | And 7 more authors.
Reproductive BioMedicine Online | Year: 2015

The aim of this study was to investigate whether a new simplified blastocyst grading system (A: fully expanded, clear inner cell mass, cohesive trophectoderm; B: not yet expanded, clear inner cell mass, cohesive trophectoderm; C: small inner cell mass ± irregular trophectoderm ± excluded/degenerate cells) was clinically useful. All day-5 single embryo transfers between 15 June 2009 and 29 June 2012 were reviewed. Implantation, clinical pregnancy and live birth rates were related to embryo quality. Five embryologists were asked to grade and decide the clinical fate of 80 images of day-5 embryos on two occasions 4-6 weeks apart. Implantation, clinical pregnancy and live birth rates decreased with deteriorating embryo quality. A highly significant (P < 0.01) difference was observed between the groups. Inter-observer agreement was substantial for grade allocation (K = 0.63) and clinical decision-making (K = 0.66). Intra-observer agreement ranged from substantial (K = 0.71) to almost perfect (K = 0.88) for grade allocation, and was almost perfect for clinical fate determination (K ≥ 0.84). This grading system is quick and easy to use, effectively predicts IVF outcome and has levels of agreement similar to, if not better than, those associated with more complex grading systems. © 2015 Reproductive Healthcare Ltd. Source

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