Twin pregnancy obtained with frozen-thawed embryos after in vitro maturation in a patient with polycystic ovarian syndrome.

PURPOSE: A twin pregnancy was obtained in a patient with polycystic ovary syndrome after the transfer of three in vitro maturation-derived day 3 embryos that has been frozen and thawed. METHODS: The patient had received mild hMG stimulation followed by hCG injection. After culture for 24-48 h, mature oocytes were fertilized by ICSI. Embryos were cultured until day 3; supernumerary embryos were cryopreserved using a slow protocol. RESULTS: Among 15 nonatretic oocytes, 9 matured, 8 were fertilized. Four embryos were transferred but they did not implant. The subsequent transfer of three frozen-thawed embryos resulted in the delivery of two healthy girls. CONCLUSIONS: These results indicate that a pregnancy could be obtained with in vitro maturation-derived day-3 frozen-thawed embryos.

Effect of endotoxin on ventilation and breath variability: role of cyclooxygenase pathway.

To evaluate the effects of endotoxemia on respiratory controller function, 12 subjects were randomized to receive endotoxin or saline; six also received ibuprofen, a cyclooxygenase inhibitor, and six received placebo. Administration of endotoxin produced fever, increased respiratory frequency, decreased inspiratory time, and widened alveolar-arterial oxygen tension gradient (all p < or = 0.001); these responses were blocked by ibuprofen. Independent of ibuprofen, endotoxin produced dyspnea, and it increased fractional inspiratory time, minute ventilation, and mean inspiratory flow (all p < or = 0.025). Endotoxin altered the autocorrelative behavior of respiratory frequency by increasing its autocorrelation coefficient at a lag of one breath, the number of breath lags with significant serial correlations, and its correlated fraction (all p < 0.05); these responses were blocked by ibuprofen. Changes in correlated behavior of respiratory frequency were related to changes in arterial carbon dioxide tension (r = 0.86; p < 0.03). Endotoxin decreased the oscillatory fraction of inspiratory time in both the placebo (p < 0.05) and ibuprofen groups (p = 0.06). In conclusion, endotoxin produced increases in respiratory motor output and dyspnea independent of fever and symptoms, and it curtailed the freedom to vary respiratory timing-a response that appears to be mediated by the cyclooxygenase pathway.

Biochemical analysis of the sperm and infertility.

The clinical value of biochemical analysis of sperm is still unclear. In this study, we evaluated the potential of several biochemical markers in the seminal plasma (zinc, citrate, acid phosphatase, fructose and neutral alpha-glucosidase) as a screening method in male infertility investigation.

Atypical hatching of a human blastocyst leading to monozygotic twinning: a case report.

OBJECTIVE: To report a case of monozygotic twinning after atypical hatching of a human blastocyst. DESIGN: Case report. SETTING: University-based IVF program. PATIENT(S): A 33-year-old woman with tubal sterility. INTERVENTION(S): Embryo transfer of a human blastocyst with atypical hatching. MAIN OUTCOME MEASURE(S): Development to the blastocyst stage, hatching process, follow-up of pregnancy. RESULT(S): Development of a monozygotic dichorial pregnancy. CONCLUSION(S): First report of an atypical hatching of a human blastocyst leading to dichorial monozygotic twinning.

Distribution and epidermal growth factor receptor expression of primordial follicles in human ovarian tissue before and after cryopreservation.

The freezing of ovarian tissue and the growth of immature oocytes from primordial follicles is an interesting concept in ovarian tissue transplantation and in-vitro fertilization. In this study, the morphology and distribution of primordial follicles were studied in ovarian tissue from 24 women before and after cryopreservation. Cryopreservation did not significantly change either the morphology or number per unit volume of morphologically normal follicles in frozen ovarian tissue. Primordial follicles were predominant, accounting for 78.6% and 82.6% of total follicles in fresh and frozen ovarian tissues respectively. The distribution of follicles was extremely uneven in ovarian tissue. A large variation in follicle numbers was observed in ovarian tissue samples from patient to patient, and even in the same patient, indicating that the number of follicles counted in one sample of ovarian tissue may not represent the number of follicles in other tissue samples. Ovarian tissue could be frozen in the form of strips instead of fragments for fast processing and better viability of ovarian tissue in cryopreservation. The number of follicles in ovarian tissue declined with the increasing age of the patients. An immunohistochemical study showed that immunoreactivity for the epidermal growth factor (EGF) receptor was detected in primordial follicles of adult ovarian tissue. EGF receptor staining was most intense in the oocytes of primordial follicles. Weak staining for EGF receptor was observed in some surrounding pregranulosa cells. Immunohistochemical staining for EGF receptor was also present in the stromal cells of ovarian tissue, but to a much lesser degree. There was no significant difference in the immunohistochemical staining for EGF receptor in ovarian tissue before and after cryopreservation.

Expression of receptors for insulin-like growth factor-I and transforming growth factor-beta in human follicles.

The in-vitro growth of immature oocytes in early follicles from cryopreserved human ovarian tissues is a new concept in in-vitro fertilization programmes for the treatment of infertile and cancer patients. To better understand the regulatory mechanism of follicular development, immunohistochemistry was used to study the expression of insulin-like growth factor (IGF) type I receptor (IGF-IR) and transforming growth factor-beta (TGFbeta) type I (TbetaR-I) and type II (TbetaR-II) receptors in fresh and frozen ovarian tissues from 14 women. Immunoreactivities for IGF-IR and TbetaR-I were present simultaneously in the oocytes of primordial, pre-antral and antral follicles. Staining for both IGF-IR and TbetaR-I was also observed in granulosa cells of primordial, pre-antral and antral follicles. IGF-IR and TbetaR-I also stained in thecal cells of pre-antral and antral follicles. Stromal cells in surrounding ovarian tissue expressed IGF-IR and TbetaR-I at various follicular stages. Unlike TbetaR-I, TbetaR-II was expressed only in the oocytes of primordial and primary follicles, and with weak staining intensity in thecal cells. No significant staining for TbetaR-II was found in oocytes and granulosa cells of antral follicles. There was no difference in staining patterns for IGF-IR, TbetaR-I and TbetaR-II between fresh and frozen ovarian tissues, indicating that cryopreservation might not significantly alter the immunoreactivities of these receptors in frozen ovarian tissue. The results suggest that IGF-I and TGFbeta may participate in the regulation of follicular growth by binding to their receptors through an autocrine or paracrine mechanism. IGF-I and TGFbeta may be useful in regulating the in-vitro or in-vivo maturation of oocytes not only in later follicles but also very early follicles, from cryopreserved ovarian tissues for clinical use in the future.

A dirty business: caring for people who are a nuisance or a danger.

This paper argues that developments in chemical, administrative and legal methods of control, once confined to the asylum, now operate over mental patients in the community. Differences between the hospital and the community have thus been eroded. This paper therefore seeks to understand how mid-twentieth century sociology, that informed an understanding of the asylum prior to its demise, can be usefully revisited to inform an understanding of the contemporary practice of community mental health nursing. It is argued that in their development, community mental health nurses (CMHNs) have endeavoured to associate themselves with the clean work of caring, rather than with the dirty work of coercive control. However, CMHNs now find themselves representing societal and psychiatric demands for the greater control of mental patients in the community to their clients. Issues of control and care (coercion and persuasion) in community mental health care nursing practice are thus considered in relation to theory regarding the imposition of power.

Gonadal cryopreservation in the young patient with gynaecological malignancy.

For patients who are planning to have chemotherapy, radiotherapy or to undergo bilateral oophorectomy, the loss of ovarian function will result in premature ovarian menopause and loss of fertility. Embryo preservation is not an option for single women or married women because delaying treatment for at least 2 months of in-vitro fertilization cycles is inappropriate and may be life-threatening. This study reports on the indications for ovarian tissue cryobanking and the state of the art of this method in preserving fertility in women with iatrogenic premature menopause.

In vitro fertilization outcome according to age and follicle-stimulating hormone levels on cycle day 3.

PURPOSE: In a retrospective study, the prognostic factors of in vitro fertilization outcome were studied in women of 39 years of age or older, with an elevated cycle day 3 follicle-stimulating hormone (FSH) level. METHODS: Ovarian stimulation was achieved with a combination of gonadotropin-releasing hormone agonist/human menopausal gonadotropin in a short protocol. All patients underwent FSH dosage on cycle day 3 prior to stimulation. The pregnancy rate was studied according to age, FSH levels, and stimulation parameters. RESULTS: There was a negative correlation between day 3 FSH levels and the number of ovocytes retrieved. Cycles canceled because of the absence of ovarian response had a significantly higher mean FSH value (18.2 mlU/ml) than cycles ending in ovocyte retrieval (14.6 mlU/ml). Patients with three or more growing follicles during stimulation achieved a significantly higher pregnancy rate per egg retrieval (16%) compared to patients with fewer than three growing follicles (6%). Eighty percent of those pregnancies were obtained during the first two IVF cycles. Even with an elevated FSH level, some patients developed three or more follicles after stimulation. In such cases, the number of embryos available for transfer was the only significant limiting factor to achieving pregnancy. CONCLUSIONS: As our results suggest, there is a discrepancy between biological and chronological ovarian age. In patients with an elevated cycle day 3 FSH level and over 40 years of age, alternatives to fertility treatments (ovum donation, adoption, or no treatment) should not be considered as first choices. Indeed, even with elevated FSH levels, a 16% pregnancy rate per egg retrieval may be obtained if three or more growing follicles can be seen during ovarian stimulation. However, in the presence of fewer than three growing follicles during ovarian stimulation, the patient should be informed about the discouraging prognosis of the running cycle.

Down-regulation of nitric oxide production by ibuprofen in human volunteers.

Ibuprofen has been shown in vitro to modulate production of nitric oxide (NO), a mediator of sepsis-induced hypotension. We sought to determine whether ibuprofen alters NO production and, thereby, vascular tone, in normal and endotoxin-challenged volunteers. Techniques for detecting NO were validated in 17 subjects infused with sodium nitroprusside, a NO donor. Then, endotoxin (4 ng/kg) or saline (vehicle alone) was administered in a single-blinded, crossover design to 12 other subjects randomized to receive either ibuprofen (2400 mg p.o.) or a placebo. Endotoxin decreased mean arterial pressure (MAP; P =.002) and increased alveolar NO flow rates (P =.04) and urinary excretion of nitrite and nitrate (P =.07). In both endotoxemic and normal subjects, ibuprofen blunted the small fall in MAP associated with bed rest (P =.005) and decreased alveolar NO flow rates (P =.03) and urinary excretion of nitrite and nitrate (P =.02). However, ibuprofen had no effect on the decrease in MAP caused by endotoxin, although it blocked NO production to the point of disrupting the normal relationship between increases in exhaled NO flow rate and decreases in MAP (P =.002). These are the first in vivo data to demonstrate that ibuprofen down-regulates NO in humans. Ibuprofen impaired the NO response to bed rest, producing a small rise in blood pressure. Although ibuprofen also interfered with the ability of endotoxin to induce NO production, it had no effect on the fall in blood pressure, suggesting that the hemodynamic response to endotoxin is not completely dependent on NO under these conditions.

Outcome of in-vitro fertilization through natural cycles in poor responders.

This prospective study examines the benefits of using natural cycles instead of stimulated cycles in poor responders to in-vitro fertilization (IVF) treatment. Eleven patients in whom puncture was cancelled or who failed to conceive because of a poor response were included in the analysis. The data for natural cycles (n = 16) were compared with data obtained during previous stimulated cycles (n = 25) in the same women. Out of 16 natural cycles, 13 (81.3%) were scheduled for oocyte retrieval compared to 13 out of 25 stimulated cycles (52%). Eighteen metaphase II oocytes were obtained during stimulated cycles, giving a 66% fertilization rate. In natural cycles, 11 metaphase II oocytes were available giving a fertilization rate of 78.6%. A mean number of 51.5 +/- 25 ampoules of gonadotrophins per cycle were used during ovarian stimulation. Three clinical pregnancies were obtained after embryo transfer in natural cycles (18.8%/started cycle) compared to none in stimulated cycles. Our findings demonstrate that an encouraging number of pregnancies can be achieved by IVF during natural cycles in poor responders to ovarian stimulation. This may not be the first approach to consider in IVF but it should be offered as an alternative after two ovarian response failures using classical protocols of stimulation.

New paradigms for medical decision support and education: the Stanford Health Information Network for Education.

The information needs of physicians are complex and ever increasing in a world of rapidly expanding medical knowledge and a practice environment where physicians are required to know and do more with shrinking resources. Current strategies for providing clinical decision support and continuing medical education have failed, in part, because they have not provided timely, easy access to information that is current, integrated with other information and the physician's workflow, and relevant to specific questions that occur during the patient encounter. Meeting these challenges involves understanding the nature of medical knowledge, the different information needs of physicians, the clinical decision-making process, and the constraints of the physicians work environment, as well as the traditional barriers to physician education. We explore the nature of some of these challenges and propose one solution in the form of a highly integrated web-based technology--The Stanford Health Information Network for Education.

An ectopic pregnancy developing in a previous caesarian section scar.

OBJECTIVE: To report the diagnosis and management of an ectopic pregnancy (EP) developing in a caesarean section scar. DESIGN: Case report. SETTING: University medical school. PATIENT(S): A patient with a previous history of two caesarean sections developing an EP. INTERVENTION(S): Methotrexate (MTX) was administered locally under ultrasonographic guidance. MAIN OUTCOME MEASURE(S): Weekly screening of blood hCG levels and yolk sac resorption by endovaginal sonography. RESULT(S): The diagnosis was suspected by vaginal echography and confirmed by magnetic resonance imaging. Local injection of KCl and MTX provoked a progressive resorption of the pregnancy. Human chorionic gonadotropin was undetectable on day 82. CONCLUSION(S): To prevent uterine rupture in cases of an EP developing in a caesarean section scar, a medical approach can be proposed.

Who's the patient here? Inpatient psychiatric rehabilitation in a state hospital setting.

1. The primary focus of psychiatric rehabilitation is on improving the competencies of persons with psychiatric disabilities. 2. Both patients and staff must change their ideas about themselves and each other before the work of rehabilitation could move forward. 3. Institutional rigidity works against psychiatric rehabilitation, with its value on individual growth and self-sufficiency.

The Stanford Health Information Network for Education: integrated information for decision making and learning.

Although multiple decision support systems have been built for physicians, efficient delivery of valid and complete medical knowledge remains an elusive goal. In this paper we describe a new project, the Stanford Health Information Network for Education (SHINE). SHINE unifies core medical resources in an intuitive interface to support clinical decision making. Included in the description is a novel paradigm for continuing medical education (CME).

Uncoupling of biological oscillators: a complementary hypothesis concerning the pathogenesis of multiple organ dysfunction syndrome.

OBJECTIVE: To present a complementary hypothesis concerning the pathogenesis of the multiple organ dysfunction syndrome. DATA SOURCES: Primary reports and reviews published in peer-reviewed medical and scientific journals. HYPOTHESIS: We suggest that healthy organs behave as biological oscillators, which couple to one another during human development, and that this orderly coupling is maintained through a communications network, including neural, humoral, and cytokine components. We suggest that the systemic inflammatory response syndrome initiates disruption of communication and uncoupling, and further suggest that progression into the multiple organ dysfunction syndrome reflects progressive uncoupling that can become irreversible. Resolution of the inflammatory response and reestablishment of the communications network are necessary but may not be, by itself, sufficient to allow organs to appropriately recouple. This hypothesis is testable using existing laboratory and clinical tools.

Experimental human endotoxemia increases cardiac regularity: results from a prospective, randomized, crossover trial.

OBJECTIVE: To determine whether human endotoxemia is associated with a loss of the physiologic beat-to-beat variability of heart rate. DESIGN: Prospective, randomized, crossover, single-blind study. SETTING: Clinical research center in a federal, nonuniversity hospital. SUBJECTS: Healthy volunteers. INTERVENTIONS: Intravenous administration of reference (Escherichia coli) endotoxin or saline placebo, with or without previous administration of oral ibuprofen. MEASUREMENTS AND MAIN RESULTS: Electrocardiograms were continuously recorded and digitized using series of 1000 beat epochs of R-R intervals over 8 hrs. Analyses included measures in the time domain (standard deviation), frequency domain (power spectra), and a measure of regularity (approximate entropy). Endotoxin administration was associated with loss of variability by all measures. This loss of variability remained significant even with administration of ibuprofen, which blocked the development of fever and endotoxin-related symptoms. CONCLUSIONS: Infusion of endotoxin into human volunteers causes loss of heart rate variability, as measured by standard deviation and power spectra, as well as an increase in heart rate regularity, as measured by approximate entropy. Changes in approximate entropy occurred earlier than changes in other heart rate variability measures and may be a useful means of detecting early sepsis. This reduction in regularity is consistent with a model in which the pathogenesis of multiple organ system dysfunction syndrome involves the physiologic uncoupling of vital organ systems.