Search PubMed⌕ Search

Biomedical subjects

R G Edwards

Publications and source records attributed to R G Edwards.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Immunohistochemical expression of endometrial proteins and pregnancy outcome in frozen embryo replacement cycles.

The expression of two endometrial proteins, pregnancy-associated endometrial alpha-2 globulin (alpha-2 PEG) and 24K protein, was examined immunohistochemically in an attempt to identify a marker or a pattern which would predict subsequent implantation. Patients who had undergone in-vitro fertilization cycles and had at least three frozen embryos were recruited into the study. They received two cycles of hormone replacement therapy. The first was a monitored cycle in which dated endometrial biopsies were taken for immunohistochemical assessment using monoclonal antibodies to alpha-2 PEG and 24K protein and also for standard histological dating. In the second cycle, the frozen-thawed embryos were replaced. The results of the monitored cycle were then correlated with the pregnancy outcome in the transfer cycle. Ten patients conceived, of whom eight had a pattern of low immunohistochemical staining of alpha-2 PEG and high immunohistochemical staining of 24K. In the 15 patients who did not conceive, four had the same endometrial protein pattern (P less than 0.05). In the 13 specimens classified as histologically in phase, 10 (71%) showed incompatible protein expression. We conclude that the pattern of expression of the endometrial proteins alpha-2 PEG and 24 K may be potentially useful to indicate a receptive endometrium. Immunohistochemistry may yield information on endometrial development which is not apparent from routine histological assessment.

Antibodies, Monoclonal↗
PubMed1992

Pronuclear, cleavage and blastocyst histories in the attempted preimplantation diagnosis of the human hydatidiform mole.

We report a study of fertilization, syngamy and embryonic development in 14 oocytes from a woman with four previous pregnancies involving complete hydatidiform moles. Serial observations of pronuclear movements and syngamy were compared to those in a group of 10 multipronucleate embryos from other patients. One embryo and possibly two others developed normally or near-normally. The others displayed immediate cleavage or had one or three pronuclei. The tripronucleate eggs displayed various anomalous forms of growth. The unipronucleate eggs passed through a double form of syngamy, which might have involved chromosome doubling, and could have developed as androgenetic diploids. We suggest a hypothesis to explain these unusual observations.

Adult↗
PubMed1991

Secondary structure and topology of human interleukin 4 in solution.

Human interleukin 4 (IL-4) has been studied by 2D and 3D NMR techniques using uniformly 15N-labeled recombinant protein. Assignment of resonances for all but 3 of the 130 residues of the recombinant protein has been achieved, enabling the secondary structure of the protein to be defined. This consists of four major alpha-helical regions and one short section of double-stranded antiparallel beta-sheet. Analysis of distance and angle restraints derived from NMR experiments has enabled the overall molecular topology to be determined. This is related to that found for other four-helix proteins but has several distinctive features including cross-linking of helices by means of three disulfide bonds and a short section of beta-sheet. The structural analysis gives support to the hypothesis that many helical cytokines have a common fold and provides a basis for understanding the biological function of IL-4.

Amino Acid Sequence↗
PubMed1991

High fecundity of amenorrhoeic women in embryo-transfer programmes.

There is uncertainty over whether the steady decline in human fertility with increasing maternal age is due to quality of the oocyte or of the endometrium. To clarify the issue age-related implantation and pregnancy rates in two embryo-transfer programmes were examined in relation to embryo quality and type of menstrual cycle. In both the UK and the US programmes rates were higher in previously amenorrhoeic (acyclic) women than in eugonadal women, irrespective of age and number of embryos replaced. Oocyte quality, as determined by age of oocyte donor, in-vitro growth of embryo, and proportion of defective embryos in culture, did not contribute to the difference, nor did type of cycle during therapy. If a uterus that has not been subjected to regular menstrual cycles is a favourable factor, a period of induced amenorrhoea might be beneficial for infertile women.

Amenorrhea↗
PubMed1991

Heterotopic pregnancies after in vitro fertilization and embryo transfer.

Seventeen cases of heterotopic pregnancies are reported among 1648 clinical pregnancies after in vitro fertilization. The high prevalence of tubal damage among IVF patients and the use of superovulation and multiple embryo transfer might predispose patients to the condition. Nine patients reported abdominal pain and vaginal bleeding, five patients did not have symptoms, and three had acute abdominal emergencies. Transvaginal ultrasonography was superior to transabdominal ultrasonography in the diagnosis of extrauterine pregnancies. The presence of an intrauterine gestation sac in a patient without symptoms should not exclude the diagnosis of a concomitant extrauterine pregnancy until the pelvis is carefully visualized. Early diagnoses of viable ectopic pregnancies before rupture abolishes mortality and morbidity and offers the chance of patient selection for conservative treatment. In two patients the extrauterine gestation sac was treated by transvaginal aspiration and injection of potassium chloride under ultrasonographic guidance. The outcome of the intrauterine pregnancy was favorable regardless of the method of treatment of the ectopic pregnancy.

Abdomen↗
PubMed1991

Edwards' syndrome after the replacement of cryopreserved-thawed embryos.

A case of Edwards' syndrome after the replacement of frozen-thawed embryos is reported. The presence of cardiac abnormalities and limb deformities raised the suspicion of chromosomal abnormality. The diagnosis of trisomy 18 was made by cytogenetic analysis of fetal blood from the umbilical vein. The chromosomal nondisjunction might have been spontaneous or because of freezing and thawing. If it occurred as a result of freezing and thawing, it is more likely that this was at the first cleavage division rather than the second meiotic division because the embryos were frozen at the late pronuclear stage. Unfortunately, there were no karyotypic markers in the couple's chromosomes to time the nondisjunction. The wisdom of using donor oocytes in an ovum donation program from patients with long-standing infertility is questioned.

Abnormalities, Multiple↗
PubMed1991

Role of embryonic factors in implantation: recent developments.

The embryonic factors influencing implantation have been studied extensively in laboratory and domestic animals, but not in primates, including humans. Species differences make extrapolation inadvisable. Embryonic factors affecting implantation include intrinsic features of the embryo, such as its genetic constitution, morphology and hatching. Abnormal genetic constitutions or unsuccessful transitions from maternal to embryonic transcription could account for many failures of early embryonic growth and implantation. Morphology per se does not greatly influence implantation, except when it reflects an abnormal genetic constitution, e.g. in severe fragmentation, although subtle effects may be detected as experimental techniques are refined. The initiation of differentiation and intraembryonic communication between cells and cell types has been studied in animal embryos. Signals must be exchanged between the embryo and the mother to ensure satisfactory implantation. These could include platelet activating factor, prostaglandins, histamine related factors, steroids, proteins, metabolic products and immune-active factors. No one factor seems to be totally responsible for alerting the mother to the presence of an embryo, and a concerted action of these and other agents is probably responsible. The process of implantation itself is poorly understood because of a lack of adequate experimental models. The expression of complementary proteins and the role of specific enzymes and markers of endometrial and embryonic competence are factors well worthy of further study. Knowledge about human implantation is increasing because of recent developments in assisted reproductive technology, and concepts arising from many years of research in animals should find clinical applications in understanding and controlling human reproduction.

Animals↗
PubMed1991

The influence of in-vitro development upon post-thaw survival and implantation of cryopreserved human blastocysts.

Blastocysts from 198 patients were frozen using glycerol as cryoprotectant. No difference in the post-thaw survival of blastocysts or implantation rates was found between 177 patients (122 transfers) with all surplus embryos cultured to blastocysts before freezing and 20 patients (12 transfers) whose embryos were considered unsuitable for freezing during cleavage and were then frozen as blastocysts. Nineteen pregnancies were achieved, of which six aborted. Pre-freezing morphology was similar in blastocysts of patients in groups 1 and 2 and did not relate to their survival after cryopreservation. A significantly lower proportion with suspected damage after thawing was present among patients becoming pregnant after transfers of single blastocysts (P less than 0.01) and implanting embryos were in general more expanded at the time of transfer. No differences were detected between blastocysts resulting in normal development and those leading to abortion. The developmental consequences of damage to human blastocysts are discussed.

Adult↗
PubMed1991

Replacement of frozen-thawed embryos in artificial and natural cycles: a prospective semi-randomized study.

This prospective partly-randomized study assessed the relative efficacy of two strategies of patient management for the replacement of frozen-thawed embryos. A luteinizing hormone-releasing hormone (LHRH) agonist was used to induce a temporary hypogonadism in a group of patients who were then prepared for implantation by endometrial priming with hormone replacement therapy (HRT): oral oestradiol valerate and then oestradiol valerate and injections of progesterone. A second group of patients had their frozen-thawed embryos replaced during their natural cycles. Of the 84 patients treated with the LHRH regimen, 80 had embryos replaced and 16 (20%) clinical pregnancies were established. Of the 78 patients treated with natural cycles, 70 had embryos replaced and 14 (20%) achieved clinical pregnancies. There were no statistical differences between the two groups in terms of age, obstetric history, duration of infertility, number of oocytes retrieved and fertilized or the number of embryos frozen following ovarian stimulation in the embryo 'generating' cycle. In terms of pregnancy rates, both protocols were equally effective. However, the LHRH-HRT protocol was of great value in the management of oligomenorrhoeic patients and in establishing standard conditions for implantation in cyclic patients.

Cryopreservation↗