Search PubMed⌕ Search

Biomedical subjects

R G Edwards

Publications and source records attributed to R G Edwards.

At least 91 records · Page 5Linked to original sources
PubMed1994

Analysis of the solution structure of human interleukin-4 determined by heteronuclear three-dimensional nuclear magnetic resonance techniques.

Human interleukin-4 (IL-4) is a member of the family of haemopoietic cytokines that modulate cell proliferation and differentiation within the immune system. It has a four-helix-bundle structure, and possesses a high degree of mobility in certain regions, notably in the two long loops running the length of the bundle in its up-up-down-down topology. Information from a variety of three-dimensional heteronuclear NMR experiments, including chemical shifts, coupling constants and NOE data, is analysed in terms of the solution structure of IL-4. In addition, structure calculations with and without specific restraints such as hydrogen bond location or torsion angle restrictions are compared in the light of the dynamic behaviour of the polypeptide chain. Particular emphasis is placed on defining the lengths and positions of secondary structure elements, and on the likely structural preferences within the less well ordered loop regions. The overall topology of IL-4 is compared with those defined in recent structure determinations of related proteins. This analysis is combined with recent mutagenesis data to propose a possible mode of interaction of IL-4 with its receptor.

Crystallography, X-Ray↗
PubMed1994

High rates of pregnancy after long-term down-regulation of women with severe endometriosis.

OBJECTIVE: The purpose of this study was to determine the effects of pituitary down-regulation for several months on the outcome of in vitro fertilization treatment in women with severe endometriosis. STUDY DESIGN: A total of 84 patients with severe endometriosis (grades III and IV) were recruited in a semirandomized prospective study; 69 of these were controls who were given a short protocol with gonadotropin-releasing hormone agonist followed by human menopausal gonadotropin and human chorionic gonadotropin to induce follicular growth. Fifteen treated patients underwent down-regulation for 2 to 7 months and then human menopausal gonadotropin and human chorionic gonadotropin to induce follicular growth. Twenty nonpregnant controls after in vitro fertilization were treated in a similar manner. RESULTS: The pregnancy rates were much high per embryo transfer, 18 of 42 (42.8%), especially in patients in whom in vitro fertilization was carried out during the fourth month of down-regulation. Pregnancy rates in the control group were 17 of 134 (12.7%) (p < 0.001). CONCLUSION: Higher rates of pregnancy are achieved after in vitro fertilization that follows long-term down-regulation in women with extensive endometriosis.

Adult↗
PubMed1994

Cumulative conception and live-birth rates after in vitro fertilization with and without the use of long, short, and ultrashort regimens of the gonadotropin-releasing hormone agonist buserelin.

OBJECTIVE: Our purpose was to compare cumulative conception and live-birth rates after in vitro fertilization with and without the use of the long, short, and ultrashort regimens of the gonadotropin-releasing hormone agonist buserelin. STUDY DESIGN: Life-table analysis of conception and live-birth rates in relation to ovarian stimulation regimen used in 2893 women who had one of five stimulation regimens exclusively throughout all treatment cycles, namely, human menopausal gonadotropin with or without clomiphene citrate; follicle-stimulating hormone with or without clomiphene citrate; and long, short, and ultrashort protocols of buserelin, plus follicle-stimulating hormone or human menopausal gonadotropin; and in an additional 347 women who had been administered both human menopausal gonadotropin and follicle-stimulating hormone with or without clomiphene citrate. RESULTS: The cumulative conception rate and cumulative live-birth rate were significantly higher in those women treated exclusively with the long buserelin regimen (59% and 55%, respectively, after three cycles) compared with those who only had human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate (39% and 29%, respectively, after three cycles) (p = 0.001 and p = 0.0001) or compared with those who had only short or ultrashort buserelin regimens (22% and 17% after two cycles) (p = 0.0001 and p = 0.005). The pregnancy failure rate in patients on the long buserelin regimen was 22.4% (95% confidence interval 14.8% to 30.0%) compared with 33.3% (95% confidence interval 29.6% to 37.0%) in those who had human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate (p = 0.03). When the probabilities of first conception and first live birth were examined by treatment regimen, after we allowed for the effects of age, cause of infertility, calendar year of treatment, and treatment cycle number (with a multiple logistic regression model), it was found that, relative to human menopausal gonadotropin or follicle-stimulating hormone with or without clomiphene citrate, the odds of conceiving with the long buserelin regimen was 1.63 (95% confidence interval 1.31 to 2.03) (p < 0.001) and the odds of a live birth was 1.97 (95% confidence interval 1.53 to 2.54) (p < 0.001). Similarly, relative to short or ultrashort buserelin the odds of conceiving with long bureselin was 1.88 (95% confidence interval 1.39 to 2.55) (p < 0.001) and the odds of a live birth was 1.79 (95% confidence interval 1.25 to 2.56) (p = 0.001). CONCLUSION: Pituitary desensitization with the long protocol of buserelin significantly increases the probabilities of conception and live birth after in vitro fertilization.

Adult↗
PubMed1994

Pregnancy and birth rates of live infants after in vitro fertilization in women with an without previous in vitro fertilization pregnancies: a study of eight thousand cycles at one center.

OBJECTIVE: Our aim was to compare the cumulative conception and live-birth rates after in vitro fertilization in women undergoing their first course of in vitro fertilization treatment with those in women undergoing their second course of treatment, having previously achieved an in vitro fertilization pregnancy. This study occurred in a tertiary referral-assisted conception unit. STUDY DESIGN: The cumulative conception rates obtained by life-table analysis in 4115 women having their first course of in vitro fertilization therapy (7327 treatment cycles leading to 1123 pregnancies) were compared by means of the log-rank test with those of 331 women in their second course of treatment, having previously achieved an in vitro fertilization pregnancy (561 treatment cycles leading to 138 second in vitro fertilization pregnancies). Similarly, the cumulative live birth rates of 3824 women in their first course of treatment (7136 treatment cycles leading to 732 live births) were compared with those of 105 women in their second course of treatment, having previously achieved an in vitro fertilization live birth (205 treatment cycles leading to 33 second in vitro fertilization live births). RESULTS: The cumulative conception rates and cumulative live birth rates were significantly higher in women having their second course of in vitro fertilization treatment than in those having their first course (cumulative conception rate: p = 0.0001; cumulative live birth rate, p = 0.007). After five cycles of in vitro fertilization, the cumulative conception rates and cumulative live birth rates were 49.8% (95% confidence interval, 46.3% to 53.5%) and 39.0% (95% confidence interval, 35.4% to 42.9%), respectively, in those having their first course of treatment compared with 69.9% (95% confidence interval, 57.6% to 81.3%) and 68.6% (95% confidence interval, 46.1% to 88.5%), respectively, in those having their second course. The estimated median numbers of cycles taken to achieve a pregnancy and live birth (assuming all women could potentially undergo the same number of cycles) were six and eight, respectively, in the first course of treatment compared with only three and five in the second course. CONCLUSION: Women who have achieved a previous in vitro fertilization pregnancy have significantly higher cumulative conception rate and cumulative live birth rates compared with those of women having their first course of treatment.

Adult↗
PubMed1994

Implantation, interception and contraception.

The factors involved in post-fertilization events leading to implantation in mammals are discussed with special reference to potential forms of interception. The stages of embryonic growth until implantation are considered initially. The growth and differentiation of the uterine endometrium is then described, followed by the events occurring during the apposition and invasion of the implanting embryo. Several potential approaches to new forms of interception are considered, and the advantages and disadvantages of each of them are evaluated. Among them, new vaccines against the zona pellucida, inactivation of the secretions of the blastocyst, hatching, the activity of pinopodes, and the endometrial proteins produced in the secretory phase seem to offer various and varied targets. Some existing methods of fertility regulation may act by affecting these stages of development, e.g. RU486 may interfere with pinopod function. Various physiological and embryonic consequences of interfering with these stages of pregnancy are discussed.

Animals↗
PubMed1994

Oocyte donation--implications for fertility treatment in the nineties.

In the past decade, oocyte donation has become a widely used assisted reproduction technique with reported pregnancy rates often higher than those for conventional in-vitro fertilization. Recipients of donated oocytes include women with premature ovarian failure or severe genetic disorders, those who respond poorly to ovarian hyperstimulation, women over 40 years of age, and, recently, postmenopausal women. The donation of oocytes to older women raises many medical and social issues which have to be addressed.

Child Advocacy↗
PubMed1993

Comparative trial between an ultra-short and long protocol of luteinizing hormone-releasing hormone agonist for ovarian stimulation in in-vitro fertilization.

A total of 312 patients with tubal infertility participated in a prospective randomized study comparing two regimens of ovarian stimulation with a luteinizing hormone-releasing hormone agonist (buserelin) and human menopausal gonadotrophin (HMG). Half of the patients were given an ultra-short treatment protocol when the agonist was administered on days 2, 3 and 4 of the stimulated cycles; the other half were given a long protocol when the agonist was administered from the mid-luteal phase of the cycle preceding the treatment cycle. The mean number of HMG ampoules used per patient was significantly higher in the long protocol. No significant differences were found between the two groups in the incidence of cancelled cycles, failed oocyte recovery, mean number of oocytes recovered per patient, complete failure of fertilization and the fertilization and embryo cleavage rate. More patients undergoing the long protocol had supernumerary embryos cryopreserved and successful deliveries.

Adult↗
PubMed1992

Cumulative conception and livebirth rates after in-vitro fertilisation.

Cumulative conception and livebirth rates related to age and cause of infertility provide the most useful estimate of success after in-vitro fertilisation (IVF), but limited data are available. It is also uncertain whether the probability of pregnancy, livebirth, and pregnancy failure changes with repeated treatment cycles. To assess the effects of patients' age and cause of infertility on these outcomes, we studied the results of 5055 consecutive IVF cycles (773 clinical pregnancies, 518 livebirths) undertaken on 2735 patients in a single IVF unit. Cumulative conception and livebirth rates were analysed by the life-table approach and differences in rates between age-groups and between causes of infertility were measured by the log-rank test and logistic regression modelling. Both conception and livebirth rates per cycle declined with age (p less than 0.001), and cumulative conception and livebirth rates after five treatment cycles were about 54% and 45%, respectively, at 20-34 years, compared with 38.7% and 28.9% at 35-39 years and 20.2% and 14.4% at greater than or equal to 40 years. The two rates were significantly different between causal groups (p less than 0.001 and p = 0.02, respectively) and were lowest in patients with male infertility or multiple infertility factors. The pregnancy failure rate was higher (p = 0.006) in women over the age of 34 years and there was a significant decline in the chances of pregnancy and livebirth per cycle with successive treatment cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Human interleukin 4. The solution structure of a four-helix bundle protein.

Heteronuclear 13C and 15N three-dimensional nuclear magnetic resonance (n.m.r.) techniques have been used to determine the solution structure of human interleukin 4, a four-helix bundle protein. A dynamical simulated annealing protocol was used to calculate an ensemble of structures from an n.m.r. data set of 1735 distance restraints, 101 phi angle restraints and 27 pairs of hydrogen bond restraints. The protein structure has a left-handed up-up-down-down topology for the four helices with the two long overhand loops in the structure being connected by a short section of irregular antiparallel beta-sheet. Analysis of the side-chains in the protein shows a clustering of hydrophobic residues, particularly leucines, in the core of the bundle with the side-chains of charged residues being located on the protein surface. The solution structure has been compared with a recent structure prediction for human interleukin 4 and with crystal structures of other helix bundle proteins.

Computer Graphics↗
PubMed1992

Obstetric outcome of in vitro fertilization pregnancies compared with normally conceived pregnancies.

OBJECTIVE: To compare the obstetric outcome of in vitro fertilization pregnancies with normally conceived pregnancies. STUDY DESIGN: The obstetric outcome of in vitro fertilization pregnancies achieved in 763 British residents at two in vitro fertilization clinics resulting in the births of 961 babies were compared by means of the relative risk statistic with a control group of naturally conceived primiparous pregnancies matched by maternal age and multiplicity of pregnancy. RESULTS: Twenty-five percent of in vitro fertilization pregnancies were multiple pregnancies. The incidence of singleton term breech presentation was similar to that among controls. As compared with controls there was an increased incidence among in vitro fertilization pregnancies of vaginal bleeding and hypertension requiring hospitalization (p less than 0.001) and cesarean births (p less than 0.001) and, among in vitro fertilization singleton pregnancies, an increased incidence of intrauterine growth retardation (p less than 0.05), placenta previa (p less than 0.05), and preterm delivery (p less than 0.001). The congenital malformation, stillbirth, and perinatal mortality rates were comparable with maternal age-standardized national rates. CONCLUSIONS: Although the majority of in vitro fertilization pregnancies have a satisfactory obstetric outcome, there are a number of increased obstetric risks that may reflect the history of infertility, the relatively high incidence of poor obstetric history, and the lower threshold for obstetric intervention in in vitro fertilization patients.

Adult↗
PubMed1992

The cumulative embryo score: a predictive embryo scoring technique to select the optimal number of embryos to transfer in an in-vitro fertilization and embryo transfer programme.

In order to achieve a clinical pregnancy rate higher than that achieved following initial adoption of in-vitro fertilization embryo transfers, more than one embryo is transferred. This has led to a substantial increase in unwanted multiple pregnancy rates with IVF as compared with natural conception. What is therefore required is a simple, clinically useful embryo scoring system, to reflect embryo developmental potential, which will enable the selection of the optimal number of embryos to transfer in order to achieve the maximum pregnancy rate with a low incidence of high order multiple pregnancies. We believe that the Cumulative Embryo Score (CES) achieves these aims. On the day of embryo transfer the grade of each embryo transferred was multiplied by the number of blastomeres to produce a score for each embryo, and summation of the scores obtained for all the embryos transferred gave the CES. The grouped pregnancy rates obtained rose as the CES increased to maximum of 42. A continued increase in the CES above 42 did not result in any further rise in the pregnancy rate. However, an analysis of all our IVF pregnancies showed that the multiple pregnancy rate continued to rise above a CES of 42. By restricting the CES per embryo transfer to 42, 78% of triplet pregnancies and 100% of the quadruplet IVF pregnancies could have been predicted and potentially avoided.

Adult↗