Serum prolactin and TSH in an in vitro fertilization population: is there a link between fertilization and thyroid function?

PURPOSE: Measurements of TSH and prolactin are generally included in the evaluation of female infertility, but their value in women coming to in vitro fertilization (IVF) has been questioned. METHODS: In this study, we sought to investigate whether prolactin or TSH, measured in 509 specimens collected prior to therapy, predicted outcome in a prospective study of couples undergoing IVF between 1994 and 2001. RESULTS: TSH was higher in women whose fertility problem was attributed to a male factor, and prolactin was lower if the measurement was taken during menses. TSH and prolactin were positively correlated (p < 0.0001). Neither TSH nor prolactin levels correlated with overall IVF outcome; however, TSH levels were significantly higher among women who produced oocytes that failed to be fertilized and this finding persisted after adjustment for several covariates, including sperm motility. Among women who had a least one oocyte inseminated, the likelihood that they would have fewer than 50% of their eggs fertilized was significantly related to higher TSH levels in a multivariate model. CONCLUSION: We conclude that TSH may predict poor fertilization in IVF and reflect the importance of thyroid hormones in oocyte physiology.

Emergency department use by adult medicaid patients after implementation of managed care.

OBJECTIVE: To determine whether the advent of a mandatory Medicaid managed care (MMC) plan had any effect on emergency department (ED) utilization by adult Medicaid patients at an urban teaching hospital. METHODS: This was a retrospective cohort study using four years of ED records encompassing the year prior to initiation of MMC (1994-95), the enrollment year (1995-96), and two years after the program had matured (1996-98). RESULTS: Total ED census declined slightly, then returned to 1995 levels. Emergency department use by MMC patients declined steadily, with the 1998 figure of 5,888 representing a 40% decline over the pre-MMC volume of 9,849. Visits by MMC patients with acute illness or injury declined by 29%; MMC low-acuity visits decreased by 43%. Medicaid managed care low-acuity after-hours/weekend visits declined by 19%, then leveled off. The MMC enrollment was stable throughout the study period. CONCLUSIONS: Mandatory managed care can be associated with considerable diminution in ED use by Medicaid patients. This decline is most pronounced in low-acuity triage categories, and least evident after hours and on weekends.

The interpretation and use of statistics in assisted reproductive technologies.

This article has discussed some of the uses and limitations of currently available statistics for ART programs. A well-known example from statistics states that flipping a coin will produce "heads" 50% of the time and "tails" 50% of the time, provided that the coin is flipped enough times. Experience also shows that the result of individual flips cannot be predicted. Similarly, in ART, statistics can only give general probabilities and not meaningful predictions of the outcome of any particular cycle. Patients should be aware of the limits of statistical analysis as it applies to their individual treatment.

Variation of docosahexaenoic acid content in subsets of human spermatozoa at different stages of maturation: implications for sperm lipoperoxidative damage.

The oxidation of phospholipid-bound docosahexaenoic acid (DHA) has been shown to be one of the major factors that limit the motile life span of sperm in vitro. Sperm samples show high cell-to-cell variability in life span and, consequently, in susceptibility toward lipid peroxidation. Therefore, we postulated that there is also cell-to-cell variability in DHA concentration in human spermatozoa. In this study, the concentration of DHA in subsets of human spermatozoa isolated by a discontinuous Percoll density gradient was determined by gas chromatography. Four subsets of human spermatozoa were isolated using a discontinuous Percoll gradient: fraction 1 was enriched in immature germ cells and immature sperm, fractions 2 and 3 contained, mostly, immature sperm with cytoplasmic droplets, and fraction 4 contained, for the most part, morphologically normal sperm, as determined by histochemical analysis. The results indicated that there were significant differences in DHA content in sperm from all 4 fractions. DHA content in sperm from fraction 1 was 2.5-fold higher than that found in fraction 4. DHA content in mouse sperm obtained from the seminiferous tubules was 3-fold higher than that found in mouse sperm obtained from the epididymis, consistent with the findings observed in ejaculated human sperm. The results of this study indicate (i) there is cell-to-cell variability in the concentration of DHA in human sperm and (ii) that there is a net decrease in DHA content in sperm during the process of sperm maturation.

Is the mouse a clinically relevant model for human fertilization failures?

This study compares failed fertilization oocytes from patients participating in an in-vitro fertilization (IVF) programme with failed fertilization oocytes from B6SJLF(1)/J mice, in order to characterize and describe the distribution of DNA in oocytes that do not undergo normal fertilization. Our goal is to evaluate the mouse IVF system as a model to gain insight into reasons for human fertilization failures. All oocytes were stained with the vital fluorescent dye, Hoechst 33342, which rapidly stains double-stranded DNA. Of the 237 human oocytes that had been scored as failed fertilization by brightfield microscopy, 61 (25.7%) showed the presence of at least one spermatozoon within the oocyte cytoplasm. In contrast, out of 69 failed fertilization mouse oocytes, only one oocyte showed the presence of a spermatozoon within its cytoplasm. Mouse failed fertilization oocytes exhibited a significantly lower internal sperm rate (P < 0.0001) than human failed fertilization oocytes. Human failed fertilization oocytes show a higher incidence of sperm penetration, but the cytoplasm fails to support pronuclear development, whereas, at least in this strain, mouse failed fertilization oocytes arise from an inability of the spermatozoa to penetrate the oocyte. This study suggests that the mouse is not a clinically relevant model for human fertilization failures.

Efficient human sperm pronucleus formation and replication in Xenopus egg extracts.

We have achieved efficient in vitro reactivation and replication of human sperm nuclei in frog egg extracts by constructing a 4-step protocol that mimics the events of fertilization and pronucleus formation in mammalian eggs. With use of this protocol, 78-97% of human sperm nuclei from fertile donors synchronously swelled and completed full genome replication in about 2 h. We document the changes in nuclear structure that accompany efficient DNA synthesis and discuss future research and potential clinical implications of this new system.

Medicare expenditures on unsuccessful out-of-hospital resuscitations.

Numerous studies have shown the futility of continued emergency department (ED) resuscitative efforts for victims of out-of hospital cardiac arrest when prehospital resuscitation has failed. Nevertheless, these patients continue to arrive in the ED, where they create a strain on resources. To assess the economic cost of this, Medicare expenditures were determined for resuscitative efforts on victims of atraumatic, out-of-hospital cardiac arrest subsequently pronounced dead in the ED. Charts of patients pronounced dead in the ED of a 65,000-visit urban teaching hospital during 1995 were reviewed. Selected patients met the following criteria: 1) Medicare recipient age 65 or over; 2) atraumatic, out-of-hospital arrest; 3) transported to the ED by an EMS crew authorized to perform advanced cardiac life support interventions. A total of 105 cases were identified that met inclusion criteria and for which Medicare had claims on file corresponding to the date of death. Ambulance service payments ranged from $105-$391; mean = $263. Physician service payments ranged from $8-$106; mean = $65. Payments for Medicare Part A (hospital facility) ranged from $59-$1,025; mean = $436. The total Medicare reimbursement was $80,197, mean = $764. This annualizes to a national expenditure projection of $58 million. Failed out-of-hospital resuscitation for Medicare patients is associated with poor outcome and high cost. Termination of these efforts in the prehospital arena is unlikely to affect outcome, and would result in considerable cost savings on physician and hospital facility charges. Compassionate protocols that recognize these principles should be developed and implemented.

Evaluation of the effects of omega-3 fatty acid-containing diets on the inflammatory stage of wound healing in dogs.

OBJECTIVES: To ascertain the effects of dietary omega-3 (n-3) fatty acids on biochemical and histopathologic components of the inflammatory stage of wound healing. ANIMALS: 30 purpose-bred Beagles. PROCEDURE: Dogs were allotted to 5 groups of 6. Each group was fed a unique dietary fatty acid ratio of omega-6 to n-3--diet A, 5.3:1; diet B, 10.4:1; diet C, 24.1:1; diet D, 51.6:1; and diet E, 95.8:1. Dogs were fed once daily for 12 weeks, then biopsy specimens were taken from 4-day-old wounds of each dog and analyzed by gas chromatography-mass spectrometry for: prostaglandin E2 (PGE2) metabolites, and ratios of omega-6 to n-3 fatty acids, arachidonic acid (AA) to eicosapentaenoic acid (EPA), adrenic acid to docosahexaenoic acid, and PGE2 to prostaglandin E3 (PGE3) metabolites. RESULTS: Qualitative analysis was carried out on AA, EPA, adrenic acid, docosahexaenoic acid, and the major metabolite from the PGE2 and PGE3 pathway. These molecules were further quantified with respect to diet to determine significant differences. By analysis of the AA-to-EPA ratio, diet A was different from diets D and E and diets B and C were different from diet E (P < 0.05). By analysis of the PGE2-to-PGE3 metabolite ratio, diet A was different from diet E (P < 0.05). Though biochemical analysis indicated dietary dependence, histopathologic data indicated no significant difference with respect to diet groups. CONCLUSION: The biochemical component of the inflammatory stage of wound healing can be manipulated by diet. CLINICAL RELEVANCE: Omega-3 fatty acid-enriched diets can be used to control inflammation associated with dermatologic conditions.

Utility of dipstick urinalysis as a guide to management of adults with suspected infection or hematuria.

BACKGROUND: This study was done to determine whether emergency department (ED) patient management decisions made on the basis of dipstick urinalysis are altered when results of urine microscopy become available. METHODS: The study population was a prospective random sample of adult ED patients who had urinalysis ordered for detection of possible urinary tract infection (UTI) or hematuria. Clinicians were given the result of the dipstick urinalysis and were asked to formulate a management plan. Urine microscopy of the same specimen was obtained later, and the clinicians were asked if management was changed after results were known. RESULTS: Of 166 urinalyses, 118 (71%) were ordered for suspected UTI, 32 (19%) for suspected hematuria, and 16 (10%) for both. Of 134 urinalyses, 58 (43%) were positive for leukocyte esterase or nitrites, and 15 of 48 (31%) were positive for blood. Microscopy prompted a management change in only 9 of 166 patients. Six changes resulted in therapy for UTI, one resulted in withholding of therapy for UTI, and two resulted in cancellation of plans for diagnostic imaging. When urinalysis was done only to detect hematuria, none of the 32 patients had a management change after microscopy. CONCLUSION: Dipstick urinalysis for blood or UTI is a reliable diagnostic test in ED patients. In 94% of patients, subsequent findings on urine microscopy did not prompt a change in management. Microscopy added nothing to dipstick results when clinicians suspected conditions causing hematuria alone. Primary use of dipstick urinalysis, with microscopy in selected cases, would likely result in considerable cost and time saving without compromising patient care.

Bedside diagnostic testing of body fluids.

Numerous bedside diagnostic modalities are appropriate for the practice of emergency medicine. The proliferation of sophisticated technology is likely to increase both the availability and accuracy of commercial testing products. If health care reform in the United States results in a relaxation of the CLIA regulations, there will be a rapid expansion of research and development aimed at the biotechnology market. How much this would pertain to hospital-based emergency practice remains to be seen. Cost containment pressures may act in both directions on the utilization of available bedside technology. Although these tests are often less expensive than centralized laboratory determinations, the ready availability of near-patient testing may result in an increase in use that negates the lower cost. As with other diagnostic modalities, a thoughtful, considered approach based on scientific evidence will be necessary to formulate the appropriate use of bedside testing in individual emergency practice settings.

Medicaid managed care and the emergency department: the first one hundred days.

Spurred by concerns over increasing costs and variable quality, public and private third-party payors are moving their subscribers into managed care plans. A central feature of many of these plans is coordination of patient care through a primary care provider (PCP). In exchange for easy access to the PCP, patients are expected to limit their use of emergency services for episodic, primary, and urgent care problems. The State of Connecticut has begun a transition from a fee-for-service Medicaid plan into a managed care product. Because many Medicaid patients had freely used emergency services under the fee-for-service arrangement, urban teaching hospital emergency departments rapidly became a focus of efforts to control cost and change care-seeking behavior. The Hartford Hospital Emergency Department (ED) began screening, education, and referral of managed Medicaid patients in the fall of 1995 and recorded experiences with patients, administrators, and health care providers involved in the implementation of the managed care program. The first 3 mo following plan implementation were chaotic and frustrating for all parties, with many difficulties due to an unprepared infrastructure. Changes in ED operations and maturation of the payor and health care provider network eventually resulted in a reasonably smooth system accompanied by reductions in ED visit volumes of at least 15%. Continual evolution of role and goals will be necessary if EDs are to maintain an active presence in a health care system dominated by managed care plans.

Establishing an NP-staffed minor emergency area.

Patients with problems of high acuity need fully trained emergency physicians and nurses. Some patients with nonurgent problems can be cared for within the emergency department (ED) in a lower-cost setting designed and staffed specifically for this purpose. Staffing a fast track or minor emergency area (MEA) with nurse practitioners (NPs) is one way to satisfy the ED's care needs. One site analysis of the effectiveness of NPs indicates that patients are satisfied with their care, that nurses' interpersonal skills are better than those of physicians, that technical skills are equivalent, that patient outcomes are equivalent or superior and that NPs improve access to care. A nurse practitioner-staffed minor emergency area provides high quality care for approximately 21% of this site's adult emergency department population. Patients are triaged based on set criteria, allowing for short treatment times. The physical layout, triage criteria, and the NPs' scope of practice in the level 1 trauma center's ED are detailed.

Changes in membrane integrity, cytoskeletal structure, and developmental potential of murine oocytes after vitrification in ethylene glycol.

A systematic approach was taken to assess and optimize a protocol for intracellular vitrification by introducing high concentrations of the cryoprotectant agent (CPA) ethylene glycol (EG) into unfertilized murine oocytes. The effects of EG on membrane integrity, microfilament organization, and developmental potential were evaluated. During exposure to 0.5-2 M EG, oocytes showed maximum shrinkage to 55.5% of the isotonic volume within the first minute and reexpanded to their initial volume within 15 min. Transferral of oocytes to higher concentrations of EG (4-8 M EG) for 1-5 min after 15 min of equilibration at 2 M EG was tolerated well. Microfilament organization appeared normal after this equilibration period. During prolonged exposure (> 5 min) to high concentrations of EG (> 4 M), membrane blebs were noticed on the surface of the cells, and microfilament distribution was disturbed. After treatment with 6 M EG and vitrification with 6 M EG + f2p40.5 M sucrose, there were no significant differences in development to the two-cell and blastocyst stages between CPA-treated, vitrified, and control oocytes. These results indicate that EG is an effective CPA for mouse oocyte vitrification protocols without any observed compromise in morphology and developmental functions.

An ultrastructural analysis of an oocyte from an in vitro fertilization patient with repeated polyspermic fertilization.

OBJECTIVE: Our goal was to determine any ultrastructural anomalies in an oocyte from a patient with a history of polyspermy. RESULTS: Ultrastructural observations of the cortical ooplasm of several oocytes from each of three control patients showed a large population of intact cortical granules. Conversely, one oocyte from a patient with repeated polyspermic fertilization contained a relative paucity of granules in the cortex. Quantitative analysis of the cortices of control oocytes indicated that there were 17.02 +/- 0.52 cortical granules present per measured field of view, compared with 4.40 +/- 2.92 granules per field in the other oocyte. CONCLUSIONS: The presence of sufficient cortical granules is necessary for normal (monospermic) fertilization to occur. When contrasted to the cortical granule population of oocytes from several control patients, the cortex of one oocyte from the other patient showed few of these organelles. Therefore, the absence of a sufficient number of granules may have precluded normal fertilization from occurring in the eggs of this patient.

Establishing an NP-staffed minor emergency area.

A nurse practitioner-staffed minor emergency area provides high quality care for approximately 21% of their adult emergency department population. Patients are triaged based on set criteria, allowing for short treatment times. The physical layout, triage criteria and the NPs' scope of practice in the Level I trauma center's ED are detailed.

Sperm morphology and in vitro fertilization outcome: a direct comparison of World Health Organization and strict criteria methodologies.

OBJECTIVE: To perform a direct comparison of two sperm morphology methodologies with regard to IVF outcome. DESIGN: Blinded comparison of two methods of morphology assessment using the same morphology slides. PATIENTS: Data were obtained from 132 couples in a consecutive series of patients undergoing IVF. MAIN OUTCOME MEASURES: Two practical end points were selected for analysis for each couple: the presence of any fertilization and the number of fertilized eggs. Normal traditional morphology was defined as > or = 40% normal forms in a sample and normal strict criteria was defined as > or = 4%. RESULTS: Traditional morphology demonstrated a higher sensitivity and negative predictive value than strict criteria (87% versus 61%, and 68% versus 36%, respectively). Positive predictive value and specificity were also numerically greater but did not reach statistical significance. Abnormal traditional morphology, but not strict criteria, was associated with reduced fertilization even among samples with normal sperm concentration and motility. Samples with normal morphology were associated with a greater number of fertilized eggs per couple than those with abnormal morphology: this difference was 3.2 fertilized eggs for traditional morphology and 1.6 for strict criteria. Overall, for samples with < 40% by traditional morphology only one case yielded more than two fertilized eggs. In contrast, up to five fertilized eggs were noted for the lowest strict criteria scores. CONCLUSIONS: Comparison of traditional morphology and strict criteria with regard to IVF outcome favored traditional morphology in several areas. In particular, low scores were more predictive of poor IVF outcome.