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Biomedical subjects

J A Collins

Publications and source records attributed to J A Collins.

At least 37 records · Page 2Linked to original sources
PubMed1998

A randomized controlled trial of three low-dose gonadotrophin protocols for unexplained infertility.

This randomized controlled trial assessed which of three low-intensity ovulation induction protocols was associated with the highest rate of cycle completion among infertile women undergoing intrauterine insemination (IUI) with their husband's spermatozoa. Sixty-three women aged < or = 42 years with normospermic partners participated in the study. The primary diagnosis of infertility was unexplained in 89% of subjects, endometriosis in 6% and tubal factor in 5%. Women were assigned to three groups according to recombinant FSH dosage: group A received two ampoules (75 IU FSH per ampoule) on cycle day 4, and one ampoule on days 6 and 8 (total four ampoules); group B received two ampoules on days 4, 6 and 8 (total six ampoules); group C received two ampoules on days 4, 6, 8 and 10 (total eight ampoules). Daily ultrasound investigations began on cycle day 9-12 and human chorionic gonadotrophin (HCG) 5000 IU was administered when one or two follicles > or = 18 mm were seen. IUI was scheduled for the next day. HCG was given and/or ovulation shown to have occurred in 88 of 109 cycles attempted (81%) with no differences among the three dose groups. Two singleton pregnancies occurred (2.3% per ovulatory cycle and 1.8% per cycle start). There were no significant differences among the three regimes in terms of cycle parameters, suggesting that an individualized and more intensive approach to ovarian stimulation is necessary for many women with unexplained infertility.

Adult↗
PubMed1998

Failure of chest X-rays to diagnose pneumothoraces after blunt trauma.

We report four cases of occult pneumothorax in patients who had suffered blunt trauma. In each case supine chest X-rays failed to diagnose an anterior pneumothorax. Subsequent spiral computerised tomography scans of the chest showed anterior pneumothoraces in all cases. In two of the cases anterior pneumothoraces were present in spite of a chest drain having been placed in the pleural cavity. We recommend the insertion of anteriorly positioned chest drains to relieve pneumothoraces in severely injured trauma patients.

Accidental Falls↗
PubMed1997

The cost of infertility diagnosis and treatment in Canada in 1995.

The objectives of this study were to estimate the direct cost of infertility management, including diagnosis and treatment, in Canada during 1995, and the relative cost per live birth by treatment category. The analysis was based on the following estimates: the prevalence of infertility in Canada in 1995; the volume and distribution of infertility services; and the effectiveness and cost of specific infertility treatments. In 1995 there were approximately 330,000 couples experiencing infertility in Canada. It is estimated that <50% (150,000) sought medical advice or treatment during that year. A total of 13 diagnostic and treatment categories account for nearly all of the treatments received, and these categories form the treatment model. The cost of treatment per live birth ranges from Cdn$650 for clomiphene treatment of unexplained infertility to Cdn$41,000 for in-vitro fertilization. For a hypothetical group of 100 couples, the annual cost of diagnosis and treatment would be Cdn$77,000 and Cdn$200,000 respectively for a total of Cdn$277,000, or an average of Cdn$2770 per couple. After 1 year of treatment, it is expected that 26 of these 100 couples would achieve a live birth. The total annual cost of infertility management in Canada, estimated to be approximately Cdn$415 million, is 0.6% of the annual cost of health care.

Adult↗
PubMed1997

The spontaneous pregnancy prognosis in untreated subfertile couples: the Walcheren primary care study.

The spontaneous pregnancy prognosis of couples in a primary care situation has never been studied. Prognostic models have been developed for referral populations only. We wished to develop a prognostic model to estimate the likelihood of live birth and the impact of prognostic factors among untreated subfertile couples in a primary care situation. With this aim, we conducted a cohort follow-up study of 726 couples in the peninsula of Walcheren, a geographically isolated, but demographically and socio-economically representative area of an industrialized Western society, The Netherlands. Of the Walcheren population, 9.9% exhibit subfertility complaints at least once during their lifetime. There were 201 live birth conceptions during 9915 months of untreated observation. The cumulative rate of conceptions leading to live births was 52.5% when all of the untreated observations were considered, and 72.0% in the subgroup of 342 couples who remained untreated throughout their follow-up. The relevant prognostic factors in this primary care subfertility population were: abnormal post-coital test, tubal defect, ovulation defect, and duration of subfertility. A prediction score based on these factors would be accurate in approximately 76-79% of cases. Live birth prognosis can be estimated with sufficient accuracy to be useful in counselling subfertility patients, and in planning clinical management.

Adolescent↗
PubMed1997

Clinical research evidence and clinical practice.

An informal survey among colleagues turns up the far-from surprising information that the average patient contact involves at least three or four judgements and decisions: judgements about aetiology and prognosis, decisions about diagnosis and therapy, and sometimes discussions about costs and side-effects. And so it goes: 20 patients a day, 60 decisions; 100 patients a week, 300 decisions. Who makes these decisions, the doctor or the patient? What factors govern the final choice in each case? Evidence-based medicine (EBM) is the factor getting a lot of attention these days, but clinical decisions depend on many different elements. Good doctors have always made use of experience and judgement as well as the best available evidence.

Clinical Medicine↗
PubMed1997

Major DNA fragmentation is a late event in apoptosis.

Apoptosis, the terminal morphological and biochemical events of programmed cell death, is characterized by specific changes in cell surface and nuclear morphology. In addition, DNA fragmentation in an internucleosomal pattern is detectable in mass cultures of apoptotic cells. However, DNA fragmentation and nuclear morphological changes may not necessarily be associated events. In this study, we examined OVCAR-3 and KB human carcinoma cells using time-lapse video phase-contrast microscopy to characterize the surface and nuclear morphological features of apoptosis in response to treatment with either taxol or ricin. The surface morphological features of apoptosis were the same in both cell types and with both drugs. Using an in situ nick-translation histochemical assay, these single cells were also examined for DNA strand breaks during apoptosis. Surface morphological changes demonstrated discrete stages of cell rounding, surface blebbing, followed by cessation of movement and the extension of thin surface microspikes, followed much later by surface blistering and cell lysis. Nuclear features examined by DAPI cytochemistry demonstrated apoptotic nuclear condensation very early in this sequence, usually at the time of initial surface blebbing. The nick-translation assay, however, demonstrated DNA strand breaks at a much later time, only after the formation of separated apoptotic bodies or after final cell lysis. This study points out the differences between surface and nuclear morphological changes in apoptosis, and the large temporal separation between nuclear morphological changes and major DNA fragmentation detectable by this in situ technique. This result suggests caution in using in situ nick-translation as a direct correlate of internucleosomal DNA fragmentation in apoptosis.

Apoptosis↗
PubMed1996

Empirical evidence of bias in infertility research: overestimation of treatment effect in crossover trials using pregnancy as the outcome measure.

OBJECTIVE: To determine whether crossover trials with simple pooling of data over different study periods leads to a different estimate of treatment effect compared with parallel group trials in infertility research using pregnancy as the outcome measure. DESIGN: An observational study using nine overviews that included trials with both crossover and parallel group designs. These overviews comprised 17 crossover and 17 parallel group trials. In total, there were 5,291 outcomes including 775 pregnancies. The association between study design and treatment effect estimate was analyzed using multiple logistic regression, controlling for differences in the therapeutic interventions and variations in the methodological quality of the trials. SETTING: Infertile patients in an academic research environment. PATIENTS: Infertile patients undergoing treatment efficacy evaluation in controlled trials. INTERVENTIONS: Random allocation to a variety of treatments including clomiphene citrate, hCG, IUI, tamoxifen, and bromocriptine. MAIN OUTCOME MEASURE: Estimate of bias between study designs, based on the interaction of study design and treatment in the logistic regression model. RESULTS: Crossover trials produced a larger average estimate of treatment effect compared with trials with a parallel group design, overestimating the odds ratio by 74% (95% confidence interval, 2% to 197%). CONCLUSION: The use of a crossover design for evaluating infertility treatments with outcomes that prevent patients from completing later phases of the trial should be avoided because it leads to exaggerated estimates of treatment effect and may result in erroneous inferences and clinical decisions. Furthermore, the type of study design should be taken into account when assessing the methodological quality of therapy trials in infertility.

Bias↗
PubMed1996

Polyploidy and failed fertilization in in-vitro fertilization are related to patient's age and gamete quality.

A review of 392 cycles of in-vitro fertilization (IVF) was carried out in order to identify whether any factors such as sperm concentration at insemination, sperm motility or morphology, oocyte grading, number of oocytes retrieved, patient age, follicular stimulation protocols or duration of follicular growth, could be associated with the incidence of polyploidy or completely failed fertilization. The majority of polypronuclear fertilizations occurred in mature oocytes and in patients < 37 years of age and the incidence of polyploidy was strongly associated with fertilization and pregnancy rates. Fertilization rates were highest with mature oocytes. A significant linear trend was observed with failed fertilization and sperm concentration, morphology and motility. High rates of failed fertilization were found in patients > 37 years of age and with one to five oocytes retrieved. No significant difference was seen in stimulation protocols and oocyte grading between oocytes that fertilized and those that did not. Cycles with good sperm morphology and motility, the presence of mature oocytes, the retrieval of a large number of oocytes and younger maternal age seem to provide the best chance for IVF success.

Adult↗
PubMed1995

An estimate of the cost of in vitro fertilization services in the United States in 1995.

OBJECTIVE: To estimate the cost of adding IVF treatment to a standard health care benefits package. In vitro fertilization cost is defined as the average charge for a single cycle of treatment in an existing IVF program. DESIGN: Cost analysis. SETTING: Two hundred sixty IVF centers active in the United States in 1993. MAIN OUTCOME MEASURES: In vitro fertilization utilization and outcomes for 1993 were estimated from data in an existing registry. In vitro fertilization charges were determined from a 1993 survey of IVF clinics. The resulting expenditures for benefits and premiums were projected to 1995 together with the additional cost if utilization were to increase by 300% or 500%. RESULTS: In the United States in 1993 there were 31,718 IVF cycles for which the average charge was $6,233, leading to a total expenditure of approximately $197.70 million for IVF services in 1993. The projected cost of adding IVF services to a typical employer health plan in 1995 would be $2.79 per annum and the premium would be $3.14. Benefits and premium costs for a 300% utilization increase were $8.37 and $9.41, respectively, and for a 500% increase, $13.95 and $15.69, respectively. CONCLUSIONS: The cost of IVF services would be a minute fraction of the annual cost of a typical family benefits program ($3,393). Savings from reduced utilization of alternative treatments would offset a portion of this increase. Increases in utilization rates should be controlled by clinical criteria.

Adolescent↗
PubMed1995

Uncovering and managing denial during the research process.

This article describes experiences of geropsychiatric nurses examining the effectiveness of the Progressively Lowered Stress Threshold Model for caregivers of persons with Alzheimer's disease and related disorders, and briefly reviews the literature on coping and denial. This research project, and those of many other psychiatric nurses, is predicated on the expectation that subjects will be able to acknowledge and report to investigators their personal and intimate responses to the challenges and everyday experiences of caregiving. Clearly, the research findings will be most valid if subjects are completely open about all aspects of their experiences, no matter how painful; yet this is often an idealized expectation. Therefore, this article also explores the concerns of geropsychiatric nurse researchers attempting to balance sensitivity to the needs of subjects and the reliability and validity of the data.

Adaptation, Psychological↗
PubMed1995

Melatonin and steroids in human pre-ovulatory follicular fluid: seasonal variations and granulosa cell steroid production.

Follicular fluid samples were obtained from the largest pre-ovulatory follicle of 120 women undergoing in-vitro fertilization and were examined for melatonin by enzyme-linked immunosorbent assay and the steroids oestradiol and progesterone by radioimmunoassay. The concentrations (mean +/- SE) of melatonin (213.4 +/- 18.9 pmol/l) and progesterone (20.1 +/- 1.1 mumol/l) in follicular fluid during the autumn and winter (dark) months were significantly higher than during the spring and summer (light) months, melatonin (138.4 +/- 12.5 pmol/l) and progesterone (11.6 +/- 0.8 mumol/l). By contrast, oestradiol concentrations were significantly lower during the dark months than during the light months (264.7 +/- 44.1 and 661.8 +/- 55.1 nmol/l respectively). There was a positive correlation between follicular fluid melatonin and progesterone concentrations (r = 0.271, P < 0.05, n = 120) and a negative relationship between melatonin and oestradiol (r = -0.254, P < 0.05, n = 120). The effects of melatonin alone and in combination with human chorionic gonadotrophin (HCG) or follicle stimulating hormone (FSH) on steroidogenesis by human granulosa cell culture were also investigated. Melatonin had minimal effects on oestradiol or progesterone production by granulosa cells. Interestingly, the oestradiol response in culture appeared to be different according to the time of the year when harvested. During the light period oestradiol production was enhanced. Melatonin also synergized with HCG in increasing progesterone production on days 6 and 7 after treatment during both light and dark periods. FSH stimulated oestradiol production by the cells on day 2 of culture. Melatonin had no effect on FSH stimulation of oestradiol production. The results of this study suggest that melatonin may be involved in the regulation of steroidogenesis by the human ovaries.

Cells, Cultured↗
PubMed1995

Randomized controlled trial of follicle stimulating hormone versus human menopausal gonadotrophin in in-vitro fertilization.

The adverse effect of raised luteinizing hormone (LH) concentrations on reproductive outcome suggests that exogenous LH administration for ovarian stimulation may not be desirable. The aim of this study was to compare the clinical pregnancy rates between follicle stimulating hormone (FSH) and human menopausal gonadotrophin (HMG) used in in-vitro fertilization (IVF) cycles. A total of 232 infertile patients, with a mean duration of infertility of 67.1 +/- 32.9 months, were selected for IVF (female age < 38 years, FSH < 15 IU/l, and total motile sperm count > 5 x 10(6)). A short (flare-up) protocol with daily leuprolide acetate was followed randomly from day 3 with FSH (n = 115) or human menopausal gonadotrophin (HMG; n = 117), at an initial dose of two ampoules per day. A maximum of three embryos was transferred, and the luteal phase was supported with four doses of HCG (2500 IU). No differences were observed between the two groups in any of the cycle response variables except fertilization rates per oocyte and per patient, both of which were significantly higher with FSH. Clinical pregnancy rates per cycle initiated, per oocyte retrieval and per embryo transfer were 19.1, 21.0 and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectively for HMG. Whilst these differences were not statistically significant, the results of this interim analysis suggest that HMG may be associated with a lower clinical pregnancy rate than FSH.

Androgens↗
PubMed1995

Natural cycles for in-vitro fertilization: cost-effectiveness analysis and factors influencing outcome.

Improvements in oocyte culture technique, sperm preparation, oocyte retrieval method and ovarian stimulation regimens have produced higher pregnancy rates with in-vitro fertilization (IVF) treatment. However, because ovarian stimulation is expensive and not without risk, there is increasing interest in the option of using natural cycles for IVF. This study was performed to document the experience and outcome in 240 natural cycles. Cancellation occurred in 28 cycles (12%), and LH surge was observed in 56 (23%), leaving 156 (65%) cycles which progressed to oocyte retrieval. No oocytes were retrieved in 26 cycles. Among the successful oocyte retrievals, the majority yielded one oocyte. There was no evidence of fertilization in 26 cases, and triploid fertilization was observed in 12 cases. Embryos suitable for transfer were available in 92 cycles in which 11 (12%) clinical pregnancies were confirmed. Despite the high failure rate at each step in the process, natural cycles are more cost-effective than stimulated cycles which incur an incremental cost per live birth of $48,000. Natural cycles offer a low-cost alternative that may be more accessible to patients.

Adult↗
PubMed1995

Pharmacological interventions for the induction of ovulation.

Ovulation induction is the most common medical intervention for the treatment of infertility. Clomifene is generally the first treatment choice for patients with amenorrhoea, unless there is profound hypothalamic deficiency. When clomifene fails to induce ovulation, menotropins (human menopausal gonadotrophin) or gonadotrophin-releasing hormone (GnRH) are effective, most notably in WHO group 1. In this condition associated with low estrogen and gonadotrophin levels, the aggregate of reported pregnancy rates is 25% per cycle. In hyperprolactinaemic anovulation bromocriptine reduces prolactin levels and thereby restores normal cyclicity. In all of the above conditions, the pharmacological agent addresses a specific defect in an explicit manner. WHO group 2 ovulatory disorders arise from hyperandrogenicity and other conditions that respond less predictably to gonadotrophin therapy. In women with WHO group 2 disorders, the aggregate of reported pregnancy rates is 8%. Ovulation induction is also used in ovulatory infertile women to generate multiple follicles and increase the likelihood of fertilisation. The aggregate of pregnancy rates in clomifene trials was 7% per cycle, and 6% in gonadotrophin trials. Gonadotrophin therapy is more effective, however, in association with assisted reproduction techniques. The contrasting treatment success in discrete disorders (25% per cycle) and heterogeneous disorders such as WHO group 2 and persistent infertility (6 to 8% per cycle) underlines the need for research to discover specific causal mechanisms and identify explicit new pharmacological interventions.

Bromocriptine↗
PubMed1995

Follicle-stimulating hormone versus human menopausal gonadotropin for in vitro fertilization cycles: a meta-analysis.

OBJECTIVE: To conduct a systematic overview of available data comparing FSH with hMG in IVF treatment cycles. DESIGN: A meta-analysis of randomized trials of FSH versus hMG use in ovarian stimulation protocols, with or without GnRH agonists, in IVF treatment cycles. Search strategies included on-line searching of the National Library of Medicine MEDLINE data base from 1975 to 1993 and hand searching of bibliographies of relevant publications and reviews and abstracts of scientific meetings. Common odds ratio (OR) and overall absolute treatment effect were calculated after demonstrating homogeneity of treatment effect across all trials. MAIN OUTCOME MEASURES: Clinical pregnancy rates per cycle start, per cycle reaching oocyte retrieval, and per cycle reaching ET. RESULTS: Eight trials met the inclusion criteria. The overall OR in favor of FSH for cycle start, oocyte retrieval, and ET were 1.71, 1.69 and 1.70, respectively, and represented an overall absolute treatment effect of 8.5%, 8.0% and 8.3%, respectively. CONCLUSIONS: This meta-analysis demonstrates that in IVF cycles the use of FSH is associated with a significantly higher clinical pregnancy rate than hMG.

Abortion, Spontaneous↗
PubMed1995

The prognosis for live birth among untreated infertile couples.

OBJECTIVE: To estimate the likelihood of live birth and the impact of prognostic factors among untreated infertile couples. DESIGN: Cohort follow-up study. SETTING: Eleven infertility clinics in academic medical centers. PATIENTS: Two thousand one hundred ninety-eight couples with infertility of > 1 year in duration. Untreated months of observations on 873 untreated couples (18,364 months) were combined with observations before the first treatment among 1,325 treated couples (9,761 months). INTERVENTIONS: Diagnostic tests as indicated. MAIN OUTCOME MEASURES: Time to conception for live birth; effect of baseline characteristics estimated by means of proportional hazards analysis. RESULTS: There were 263 live birth conceptions during 28,125 months of untreated observations. The cumulative rate of conceptions leading to live birth was 14.3% at 12 months. The relevant prognostic factors were pregnancy history, duration of infertility, female partner's age, male defect, endometriosis, and tubal disease. A prediction score based on these factors would be accurate in approximately 62% of cases. CONCLUSIONS: The estimation of live birth among untreated infertile couples is sufficiently accurate to be useful in the clinical management of infertility and in the planning of clinical trials.

Adult↗
PubMed1995

[A randomized, controlled trial comparing follicle stimulating hormone (FSH) to human menopausal gonadotropin (hMG) in fertilization in vitro].

The adverse effect of raised luteinizing hormone (LH) concentrations on reproductive outcome suggests that exogenous LH administration for ovarian stimulation may not be desirable. The aim of this study was to compare the clinical pregnancy rates between follicle stimulating hormone (FSH) and human menopausal gonadotrophin (HMG) used in in-vitro fertilization (IVF) cycles. A total of 232 infertile patients, with a mean duration of infertility of 67.1 +/- 32.9 months, were selected for IVF (female age < 38 years, FSH < 15 IU/l, and total motile sperm count > 5 x 10(6). A short (flare-up) protocol with daily leuprolide acetate was followed randomly from day 3 with FSH (n = 115) or human menopausal gonadotrophin (HMG; n = 117), at an initial dose of two ampoules per day. A maximum of three embryos was transferred, and the luteal phase was supported with four doses of HCG (2,500 IU). No differences were observed between the two groups in any of the cycle response variables except fertilization rates per oocyte and per patient, both of which were significantly higher with FSH. Clinical pregnancy rates per cycle initiated, per oocyte retrieval and per embryo transfer were 19.1, 21.0 and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectively for HMG. Whilst these differences were not statistically significant, the results of this interim analysis suggest that HMG may be associated with a lower clinical pregnancy rate than FSH.

Adult↗