Predicting the likelihood of live birth for elective oocyte cryopreservation: a counseling tool for physicians and patients.

Study question: Can a counseling tool be developed for women desiring elective oocyte cryopreservation to predict the likelihood of live birth based on age and number of oocytes frozen? Summary answer: Using data from ICSI cycles of a population of women with uncompromised ovarian reserve, an evidence-based counseling tool was created to guide women and their physicians regarding the number of oocytes needed to freeze for future family-building goals. What is known already: Elective oocyte cryopreservation is increasing in popularity as more women delay family building. By undertaking elective oocyte freezing at a younger age, women hope to optimize their likelihood of successful live birth(s) using their thawed oocytes at a future date. Questions often arise in clinical practice regarding the number of cryopreserved oocytes sufficient to achieve live birth(s) and whether or not additional stimulation cycles are likely to result in a meaningful increase in the likelihood of live birth. As relatively few women who have electively cryopreserved oocytes have returned to use them, available data for counseling patients wishing to undergo fertility preservation are limited. Study design, size, duration: A model was developed to determine the proportion of mature oocytes that fertilize and then form blastocysts as a function of age, using women with presumably normal ovarian reserve based on standard testing who underwent ICSI cycles in our program from January, 2011 through March, 2015 (n = 520). These included couples diagnosed exclusively with male-factor and/or tubal-factor infertility, as well as cycles utilizing egg donation. Age-specific probabilities of euploidy were estimated from 14 500 PGS embryo results from an external testing laboratory. Assuming survival of thawed oocytes at 95% for women <36 y and for egg donors, and 85% for women ≥36 y, and 60% live birth rate per transferred euploid blastocyst, probabilities of having at least one, two or three live birth(s) were calculated. Participants/materials, setting, method: First fresh male-factor and/or tubal-factor only autologous ICSI cycles (n = 466) were analyzed using Poisson regression to calculate the probability that a mature oocyte will become a blastocyst based on age. Egg donation cycles (n = 54) were analyzed and incorporated into the model separately. The proportion of blastocysts expected to be euploid was determined using PGS results of embryos analyzed via array comparative genomic hybridization. A counseling tool was developed to predict the likelihood of live birth, based on individual patient age and number of mature oocytes. Main results and the role of chance: This study provides an evidence-based model to predict the probability of a woman having at least one, two or three live birth(s) based on her age at egg retrieval and the number of mature oocytes frozen. The model is derived from a surrogate population of ICSI patients with uncompromised ovarian reserve. A user-friendly counseling tool was designed using the model to help guide physicians and patients. LIMITATIONS, REASONS FOR CAUTION: The data used to develop the prediction model are, of necessity, retrospective and not based on patients who have returned to use their cryopreserved oocytes. The assumptions used to create the model, albeit reasonable and data-driven, vary by study and will likely vary by center. Centers are therefore encouraged to consider their own blastocyst formation and thaw survival rates when counseling patients. Limitations, reasons for caution: Our model will provide a counseling resource that may help inform women desiring elective fertility preservation regarding their likelihood of live birth(s), how many cycles to undergo, and when additional cycles would bring diminishing returns. Study funding/competing interests: None. Trial registration number: Not applicable.

Building a model to increase live birth rate through patient-specific optimization of embryo transfer day.

PURPOSE: Many practices are moving away from cleavage-stage transfer in favor of blastocyst transfer. The purpose of this study is to evaluate how the overall live birth rate for fresh IVF cycles may increase by optimizing the day of transfer for each patient. METHODS: This is a retrospective cohort study of 1225 first fresh autologous IVF cycles performed between May 2012 and November 2013. Stepwise logistic regression was used to determine characteristics associated with live birth following cleavage-stage versus blastocyst transfer. The optimal transfer day (i.e., the day that maximized the odds of live birth) was determined for each patient, and the actual live birth rate was compared with the projected rate had each patient undergone transfer on her optimal day. RESULTS: With transfer on the optimal day for each patient, the overall birth rate would have increased from its actual value of 34.8 % to a projected 43.0 %, a 24 % increase. The majority of this increase (21 %) was due to optimization of patients who underwent cleavage-stage transfer but had a higher projected birth rate from blastocyst transfer. These patients were older (37.8 versus 36.0 years, p < 0.01) and had more follicles ≥18 mm than patients who should have remained with a cleavage-stage transfer. CONCLUSIONS: A model can be built enabling patient-specific identification of optimal transfer day; within this discovery cohort, such optimization was estimated to increase live birth following a fresh transfer by 24 %. This study suggests blastocyst transfer should be more widely offered; however, there remain patients for whom a cleavage-stage transfer may yield better outcomes.

Are women with obesity and infertility willing to attempt weight loss prior to fertility treatment?

OBJECTIVE: To assess attitudes towards weight loss interventions in patients seeking infertility treatment. METHODS: We evaluated prior weight loss experiences, attitudes towards future interventions by body mass index (BMI), and willingness to delay fertility treatment for weight loss interventions stratified by BMI using logistic regression amongst women ≤45years old with infertility over three months or recurrent pregnancy loss. RESULTS: The average age of our convenience sample of respondents (148 of 794 eligible women, 19%) was 34.5 years old, with a mean BMI of 26.7±7.4kg/m2, including 37 with a BMI >30kg/m2 (25%). Most women had attempted conception over 1year. The majority of women with overweight or obesity were attempting weight loss at the time of survey completion (69%). While 47% of these women reported interest in a supervised medical weight loss program, 92% of overweight women and 84% of women with obesity were not willing to delay fertility treatment more than 3 months to attempt weight loss. CONCLUSION: Most women with obesity and infertility in our population are unwilling to postpone fertility treatment for weight loss interventions.

Correlation between microsomal (Na+ + K+)-ATPase activity and [3H]ouabain binding to heart tissue homogenates.

ATP plus Mg2+ plus Na+ supported [3H]ouabain binding to canine left ventricular tissue homogenates and microsomal (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) activity from the same tissue were measured. A linear relationship was found between the initial velocity of [3H]ouabain binding to tissue homogenates and microsomal (Na+ + K+)-ATPase activity from the same tissue in the presence and absence of in vivo bound digoxin. In vivo bound digoxin reduced both measurements. With tissue from digoxin-free hearts, a linear relationship was also obtained between the initial velocity and the maximum level of [3H]ouabain binding to tissue homogenate. Binding of [3H]ouabain to whole tissue homogenate is a convenient method for estimating (Na+ + K+)-ATPase activity in small left ventricular biopsy samples.

Effect of chronic potassium depletion on digitalis-induced inotropy and arrhythmias.

The arrhythmogenic and inotropic effects of digoxin were studied in normokalemic controls, chronically hypokalaemic, and potassium-repleted dogs instrumented to maintain heart rate, mean aortic pressure, mean left atrial pressure and autonomic tone constant. The duration of digoxin infusion needed to produce ventricular tachycardia (VT) was 56.7 +/- 3.6 min in depleted dogs, 69.0 +/- 2.7 min in controls (P less than 0.005 compared with depleted dogs), and 60.5 +/- 3.0 min in repleted dogs. Baseline left ventricular dP/dt (LV dP/dt) was similar in all groups. After digoxin, LV dP/dt increased more in controls and repleted dogs than in chronically hypokalaemic dogs; eg, after 45 min of digoxin infusion LV dP/dt increased 12.7 +/- 4.4% in hypokalaemic dogs; eg, after 45 min of digoxin infusion LV dP/dt increased 12.7 +/- 4.4% in hypokalaemic dogs, 43.8 +/- 3.3% in controls (P less than 0.025) and 39.3 +/- 8.5% in repleted dogs (P less than 0.025). The inotropic response to isoprenaline was also attenuated in the chronically hypokalaemic dogs. Plasma digoxin was similar in all groups. LV digoxin was also similar in control and depleted dogs. Although inhibition of Na+, K+-ATPase and the initial velocity of 3[H]-ouabain specific binding was less in depleted dogs at VT than in controls (P less than 0.05), the magnitude of this difference was not sufficient to explain the attenuated inotropic response. No histological abnormalities were seen on light or electron microscopy in any of the groups. Therefore chronic hypokalaemia has two deleterous effects. It increases sensitivity to the arrhythmogenic effects of digoxin and impairs the inotropic response to digoxin, and isoprenaline.

Dose response in vivo to digoxin in normo-and hyperkalaemia: associated biochemical changes.

The effect of digoxin, at two different inotropic levels, was examined in normo- and hyperkalaemic dogs. For similar inotropic responses, normo- and hyperkalaemic dogs had similar levels of (Na+, K+)-ATPase inhibition and microsomal-bound digoxin.

Effects of digitalis on normal and abnormal left ventricular segmental dynamics.

To study the effects of digoxin on regional left ventricular performance, continuous ventricular dynamics were assessed in nine patients with stable coronary disease. Computer-assisted analysis of the fluoroscopic motion of surgically implanted mid wall myocardial markers was used. The markers define six minor ventricular radii and outline the left ventricle. One and one-half hours after administration of 1 mg of intravenous digoxin, mean velocity of circumferential fiber shortening for all segments increased 19 percent, from 0.67 +/- 0.06 to 0.78 +/- 0.06 circumference/sec (P less than 0.01) and ejection fraction increased 4.5 percent, from 0.50 +/- 0.03 to 0.53 +/- 0.03 (P less than 0.05). Segmental velocity of circumferential fiber shortening, total segmental shortening and early segmental systolic shrtening increased in 83 percent to 91 percent of normal segments, depending on which index was used. Only 45 to 55 percent of initially abnormal segments benefited from digoxin. In general, segmental dyssynergy increased even when net ventricular function was enhanced. These results suggest that in pateints with chronic left ventricular contraction abnormalities due to coronary disease, deterioration of performance in abnormal regions after administration of digoxin may result from increased stress imposed by increased afterload and by improved segmental dynamics in more normal areas.

Mechanisms of and facility types involved in hazardous materials incidents.

The purpose of this study was to systematically investigate hazardous materials (hazmat) releases and determine the mechanisms of these accidents, and the industries/activities and chemicals involved. We analyzed responses by Massachusetts' six district hazmat teams from their inception through May 1996. Information from incident reports was extracted onto standard coding sheets. The majority of hazardous materials incidents were caused by spills, leaks, or escapes of hazardous materials (76%) and occurred at fixed facilities (80%). Transportation-related accidents accounted for 20% of incidents. Eleven percent of hazardous materials incidents were at schools or health care facilities. Petroleum-derived fuels were involved in over half of transportation-related accidents, and these accounted for the majority of petroleum fuel releases. Chlorine derivatives were involved in 18% of all accidents and were associated with a wide variety of facility types and activities. In conclusion, systematic study of hazardous materials incidents allows the identification of preventable causes of these incidents.

Incorporating an environmental/occupational medicine theme into the medical school curriculum.

Medical schools have been slow in teaching students how to recognize and intervene in occupationally and environmentally related illnesses. In this article, we report on the efforts at one medical school, in which an occupational medicine physician teamed with medical school educators developed, implemented, and evaluated an environmental/occupational medicine (EOM) curriculum that was introduced in several locations, using a thematic approach. This effort resulted in new EOM content being added to eight core courses in a developmental sequence and the creation of several elective experiences. We describe techniques and strategies that might be useful at other institutions in promoting the EOM theme and improving communication. Occupational/environmental physicians and educators can play leadership roles in raising interest in EOM within the medical school setting and in developing and implementing an EOM curriculum.

Methods of prioritizing and measuring occupational health risks utilizing hospital back injury data. Development of composite comparative statistics.

The employee health service of a Boston hospital wanted a method to prioritize the risk of occupational injury or illness among its employees as the first step in developing a comprehensive ergonomics program. Data from the safety office and workers' compensation third-party administrator (TPA) was combined with hospital payroll data to create rates that compared all work areas based on the common denominator of 100 full-time equivalents (FTE). Rates for four different aspects of injury experience were calculated: incidence of total reported injuries, incidence of serious injuries, level of severity of injuries, and cost. The use of these simple rates alone was inadequate to accurately prioritize risk. Because most work areas ranked differently from one rate scale to the next, it was unclear which, if any, single rate most accurately defined risk. Composite statistics that combined all of the rates were needed. The Composite Risk Indicator (CRI), the Average Relative Risk (ARR), and the Justified Average Relative Risk (JARR) were developed and examined for their utility. The JARR emerged as the best choice in this setting because it captured all available information about injury or illness experience and provided a meaningful single indicator of risk that could be followed over time.

Prioritizing back injury risk in hospital employees: application and comparison of different injury rates.

To identify high risk areas for back injury in a large teaching hospital, we calculated standard injury rates and newly developed composite statistics for nursing and non-nursing work groups. Data were extracted from the hospital's workers' compensation database. The hospital-wide total injury rate was 4.6 reports per 100 full-time equivalents (FTE); Compensation Case Rate, 1.4 cases per 100 FTE; Compensation Severity Rate, 76 days lost per 100 FTE; and the Cost Rate, $3742 per 100 FTE. The Total Injury Reports Rate for nursing varied from 14.2 per 100 FTE for Intensive Care Unit (ICU) Nursing to 3.8 per 100 FTE for Pediatric Nursing. Non-nursing areas also demonstrated increased rates for back injury. Individual statistical rates ranked areas differently in risk, whereas composite statistical measures consistently ranked ICU Nursing, Buildings and Grounds, and Orthopedics/Neurological Nursing as the top three. Patient handling was the precipitating event in the majority of nursing back injuries, indicating the need for ergonomic intervention. The use of combined statistical measures provided a more integrative measure for describing and following back injury risk over time.

Use of a job-exposure matrix to assess occupational exposures in relation to birth defects.

Accurate exposure assessment remains a challenge in occupational epidemiology. We evaluated one approach, use of a job-exposure matrix (JEM), by applying the National Institute for Occupational Safety and Health (NIOSH) JEM to a large case-control birth defects study that included parental occupation information. We investigated the JEM exposure predictions in several ways and found that for a substantial proportion of the parents in the birth defects study, the JEM yielded either no exposure data or nonsense predictions. Among exposure predictions that were plausible, most were of low probability. The high probability exposure predictions were statistically unstable, and neither low nor high probability exposure predictions were reliable. There was considerable discrepancy between the JEM predictions and expert assessments for five exposures of interest. Application of the NIOSH JEM to the birth defects study database (and probably other databases as well) does not provide a useful means of assessing occupational exposures.

Hemodynamics, renal function, plasma renin, and aldosterone in man after 5 to 14 days of bedrest.

Continous bedrest for 5 to 14 days had no significant effect on resting heart rate, blood pressure or cardiac output in six normal men. Head-up tilt induced greater tachycardia in 5 of 6 patients after bed rest than in the control period. Propranolol diminished both the tachycardia and the incidence of hypotension and faintness in upright posture. Body weight, serum electrolytes and resting renal plasma flow, and glomerular filtration rate were unchanged by bedrest. Plasma volume fell, extracellular fluid volume increased, and plasma renin activity was significantly elevated following bedrest. Unusually large increases in plasma renin followed head-up tilt or administration of isoproterenol during bedrest, and after resuming normal activity. During bedrest, plasma aldosterone was often increased in the early morning. We conclude that after bedrest, upright posture evokes strong beta-adrenergic activity, with exaggerated metabolic and circulatory responses which can be reduced or abolished by the beta-adrenergic blocker, propranolol.

Medical surveillance in the biotechnology industry.

A medical program appropriate for employees in biomedical laboratories should be based upon specific understanding of the risks and hazards associated with the work activities. Components of a medical program might include: preplacement examinations, periodic monitoring evaluations, tracking of prolonged or unusual illness, specific illness or exposure-related evaluations, epidemiological studies, immunization programs, and exit (or termination) evaluations.

General occupational health history and examination.

This paper presents a method for developing occupational medical examinations using the preplacement examination (PPE) and the periodic monitoring examination (PME). The steps for developing an appropriate PPE include goal definition, analysis of job requirements and potential exposures, an occupational and medical history, and a targeted physical examination derived from the preceding steps. The PPE should result in the proper placement of the worker. It also serves as a baseline for comparison to future testing or health-related developments. The PME checks the effectiveness of more primary preventive measures such as plant engineering controls and personal protection. The contents and frequency of the PME depend on the pathophysiology and toxicology of the hazardous exposures, the interval exposure and medical history, and legal requirements. Individual and group results should be assessed periodically for trends suggesting work-related problems that would need further evaluation.